Chapter 4 : The Memory Immune Response to Tuberculosis

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is one of the most successful pathogens with approximately 30% of the world’s population harboring the bacterium. Although some highly exposed individuals appear resistant to infection with ( ), once an individual is infected, there is little evidence that the ensuing immune response leads to sterilizing immunity ( ). Instead, the majority of individuals infected with (>90%) develop an asymptomatic chronic tuberculosis (TB) infection known as latent TB. During latent infection, activated host immune cells result in arrest of mycobacterial growth and control of disease progression. Active disease can develop from latent infection if the immune response is sufficiently suppressed, and, over their lifetime, this will occur in 5 to 10% of the latently infected individuals ( ).

Citation: Kirman J, Henao-Tamayo M, Agger E. 2017. The Memory Immune Response to Tuberculosis, p 95-115. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0009-2016
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Figure 1

Three proposed models for memory T cell differentiation. In the linear differentiation model, self-renewing memory T cells differentiate directly from effector T cells. In the progressive differentiation model, the degree of activation dictates the outcome, with highly activated cells developing into terminally differentiated effector cells and moderately activated cells developing into memory T cells with the capacity to differentiate into effector cells upon further stimulation. In the divergent model, T cell fate is determined through asymmetric cell division resulting in daughter cells that are destined to become either effector or memory T cells. These methods of T cell differentiation may coexist.

Citation: Kirman J, Henao-Tamayo M, Agger E. 2017. The Memory Immune Response to Tuberculosis, p 95-115. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0009-2016
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Figure 2

T cell memory phenotypes. After effector immunity is established, several memory populations are generated. T cells, which are CD62L and CCR7, reside predominantly in the lymphoid organs. T, CD62L, and CCR7 are found mostly in peripheral tissues, including the lung, and can recirculate. T cells are CD69, CD62L, and CCR7 and are found permanently in the lung. Finally, more recently, T cells have been described; they are CD62L and CXCR3. Other cell markers have been associated with some phenotypes specifically in tuberculosis infection; these are described in the table inset.

Citation: Kirman J, Henao-Tamayo M, Agger E. 2017. The Memory Immune Response to Tuberculosis, p 95-115. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0009-2016
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Figure 3

CD4 T helper subsets and their effector cytokines involved in immune protection against . After exposure to in the lung, dendritic cells bearing antigen stimulate naive CD4 T cells in the draining lymph nodes. Activated T cells differentiate in single- or multicytokine-producing cells, depending on the cytokine milieu at the time of activation. Effector cells migrate through the pulmonary vasculature into the lung where they produce effector cytokines that promote the antimycobacterial activity of infected cells. Multicytokine-producing CD4 T cells are thought to be more potent producers of cytokine than single-cytokine-producing cells.

Citation: Kirman J, Henao-Tamayo M, Agger E. 2017. The Memory Immune Response to Tuberculosis, p 95-115. In Jacobs, Jr. W, McShane H, Mizrahi V, Orme I (ed), Tuberculosis and the Tubercle Bacillus, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TBTB2-0009-2016
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1. Verrall AJ,, Netea MG,, Alisjahbana B,, Hill PC,, van Crevel R . 2014. Early clearance of Mycobacterium tuberculosis: a new frontier in prevention. Immunology 141 : 506 513. [CrossRef] [PubMed]
2. Huynh KK,, Joshi SA,, Brown EJ . 2011. A delicate dance: host response to mycobacteria. Curr Opin Immunol 23 : 464 472. [CrossRef] [PubMed]
3. Comstock GW,, Livesay VT,, Woolpert SF . 1974. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol 99 : 131 138.
4. Trunz BB,, Fine P,, Dye C . 2006. Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet 367 : 1173 1180. [CrossRef]
5. Anonymous . 1999. Fifteen year follow up of trial of BCG vaccines in south India for tuberculosis prevention. Tuberculosis Research Centre (ICMR), Chennai. Indian J Med Res 110 : 5669.[PubMed]
6. Colditz GA,, Berkey CS,, Mosteller F,, Brewer TF,, Wilson ME,, Burdick E,, Fineberg HV . 1995. The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 96 : 29 35.[PubMed]
7. Bogunovic D,, Byun M,, Durfee LA,, Abhyankar A,, Sanal O,, Mansouri D,, Salem S,, Radovanovic I,, Grant AV,, Adimi P,, Mansouri N,, Okada S,, Bryant VL,, Kong XF,, Kreins A,, Velez MM,, Boisson B,, Khalilzadeh S,, Ozcelik U,, Darazam IA,, Schoggins JW,, Rice CM,, Al-Muhsen S,, Behr M,, Vogt G,, Puel A,, Bustamante J,, Gros P,, Huibregtse JM,, Abel L,, Boisson-Dupuis S,, Casanova JL . 2012. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science 337 : 1684 1688. [CrossRef]
8. Flynn JL,, Chan J,, Triebold KJ,, Dalton DK,, Stewart TA,, Bloom BR . 1993. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178 : 2249 2254. [CrossRef]
9. Pape JW,, Liautaud B,, Thomas F,, Mathurin JR,, St Amand MM,, Boncy M,, Pean V,, Pamphile M,, Laroche AC,, Johnson WD Jr . 1983. Characteristics of the acquired immunodeficiency syndrome (AIDS) in Haiti. N Engl J Med 309 : 945 950. [CrossRef] [PubMed]
10. Orme IM . 1988. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection. J Immunol 140 : 3589 3593.[PubMed]
11. McShane H,, Pathan AA,, Sander CR,, Keating SM,, Gilbert SC,, Huygen K,, Fletcher HA,, Hill AV . 2004. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 10 : 1240 1244. [CrossRef]
12. Tameris MD,, Hatherill M,, Landry BS,, Scriba TJ,, Snowden MA,, Lockhart S,, Shea JE,, McClain JB,, Hussey GD,, Hanekom WA,, Mahomed H,, McShane H , MVA85A 020 Trial Study Team . 2013. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381 : 1021 1028. [CrossRef]
13. Darrah PA,, Patel DT,, De Luca PM,, Lindsay RW,, Davey DF,, Flynn BJ,, Hoff ST,, Andersen P,, Reed SG,, Morris SL,, Roederer M,, Seder RA . 2007. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major . Nat Med 13 : 843 850. [CrossRef]
14. Henao-Tamayo M,, Ordway DJ,, Orme IM . 2014. Memory T cell subsets in tuberculosis: what should we be targeting? Tuberculosis (Edinb) 94 : 455 461. [CrossRef] [PubMed]
15. Lefford MJ . 1975. Transfer of adoptive immunity to tuberculosis in mice. Infect Immun 11 : 1174 1181.[PubMed]
16. Gallegos AM,, van Heijst JW,, Samstein M,, Su X,, Pamer EG,, Glickman MS . 2011. A gamma interferon independent mechanism of CD4 T cell mediated control of M. tuberculosis infection in vivo. PLoS Pathog 7 : e1002052.[CrossRef]
17. Vogelzang A,, Perdomo C,, Zedler U,, Kuhlmann S,, Hurwitz R,, Gengenbacher M,, Kaufmann SH . 2014. Central memory CD4+ T cells are responsible for the recombinant Bacillus Calmette-Guérin ΔureC::hly vaccine’s superior protection against tuberculosis. J Infect Dis 210 : 1928 1937. [CrossRef]
18. Jung YJ,, Ryan L,, LaCourse R,, North RJ . 2005. Properties and protective value of the secondary versus primary T helper type 1 response to airborne Mycobacterium tuberculosis infection in mice. J Exp Med 201 : 1915 1924. [CrossRef]
19. Verver S,, Warren RM,, Beyers N,, Richardson M,, van der Spuy GD,, Borgdorff MW,, Enarson DA,, Behr MA,, van Helden PD . 2005. Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med 171 : 1430 1435. [CrossRef]
20. Marx FM,, Dunbar R,, Enarson DA,, Williams BG,, Warren RM,, van der Spuy GD,, van Helden PD,, Beyers N . 2014. The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study. Clin Infect Dis 58 : 1676 1683. [CrossRef]
21. Henao-Tamayo M,, Obregón-Henao A,, Ordway DJ,, Shang S,, Duncan CG,, Orme IM . 2012. A mouse model of tuberculosis reinfection. Tuberculosis (Edinb) 92 : 211 217. [CrossRef] [PubMed]
22. Neuenhahn M,, Busch DH . 2013. Whole-body anatomy of human T cells. Immunity 38 : 10 12. [CrossRef]
23. Seder RA,, Ahmed R . 2003. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 4 : 835 842. [CrossRef] [PubMed]
24. van Leeuwen EM,, Sprent J,, Surh CD . 2009. Generation and maintenance of memory CD4(+) T Cells. Curr Opin Immunol 21 : 167 172. [CrossRef] [PubMed]
25. Wolf AJ,, Desvignes L,, Linas B,, Banaiee N,, Tamura T,, Takatsu K,, Ernst JD . 2008. Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs. J Exp Med 205 : 105 115. [CrossRef]
26. Hand TW,, Kaech SM . 2009. Intrinsic and extrinsic control of effector T cell survival and memory T cell development. Immunol Res 45 : 46 61. [CrossRef] [PubMed]
27. Hou S,, Hyland L,, Ryan KW,, Portner A,, Doherty PC . 1994. Virus-specific CD8+ T-cell memory determined by clonal burst size. Nature 369 : 652 654. [CrossRef] [PubMed]
28. Welsh RM,, Selin LK,, Razvi ES . 1995. Role of apoptosis in the regulation of virus-induced T cell responses, immune suppression, and memory. J Cell Biochem 59 : 135 142. [CrossRef] [PubMed]
29. Behar SM,, Carpenter SM,, Booty MG,, Barber DL,, Jayaraman P . 2014. Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: immunity interruptus. Semin Immunol 26 : 559 577. [CrossRef]
30. Löhning M,, Hegazy AN,, Pinschewer DD,, Busse D,, Lang KS,, Höfer T,, Radbruch A,, Zinkernagel RM,, Hengartner H . 2008. Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors. J Exp Med 205 : 53 61. [CrossRef] [PubMed]
31. Ahmed R,, Bevan MJ,, Reiner SL,, Fearon DT . 2009. The precursors of memory: models and controversies. Nat Rev Immunol 9 : 662 668. [CrossRef] [PubMed]
32. Roychoudhuri R,, Lefebvre F,, Honda M,, Pan L,, Ji Y,, Klebanoff CA,, Nichols CN,, Fourati S,, Hegazy AN,, Goulet JP,, Gattinoni L,, Nabel GJ,, Gilliet M,, Cameron M,, Restifo NP,, Sékaly RP,, Flatz L . 2015. Transcriptional profiles reveal a stepwise developmental program of memory CD8(+) T cell differentiation. Vaccine 33 : 914 923. [CrossRef]
33. Arsenio J,, Metz PJ,, Chang JT . 2015. Asymmetric cell division in T lymphocyte fate diversification. Trends Immunol 36 : 670 683. [CrossRef] [PubMed]
34. Sallusto F,, Lenig D,, Förster R,, Lipp M,, Lanzavecchia A . 1999. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401 : 708 712. [CrossRef]
35. Masopust D,, Vezys V,, Marzo AL,, Lefrançois L . 2001. Preferential localization of effector memory cells in nonlymphoid tissue. Science 291 : 2413 2417. [CrossRef] [PubMed]
36. Reinhardt RL,, Khoruts A,, Merica R,, Zell T,, Jenkins MK . 2001. Visualizing the generation of memory CD4 T cells in the whole body. Nature 410 : 101 105. [CrossRef] [PubMed]
37. Ebert LM,, Schaerli P,, Moser B . 2005. Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues. Mol Immunol 42 : 799 809. [CrossRef] [PubMed]
38. Cruz A,, Torrado E,, Carmona J,, Fraga AG,, Costa P,, Rodrigues F,, Appelberg R,, Correia-Neves M,, Cooper AM,, Saraiva M,, Pedrosa J,, Castro AG . 2015. BCG vaccination-induced long-lasting control of Mycobacterium tuberculosis correlates with the accumulation of a novel population of CD4 +IL-17 +TNF +IL-2 + T cells. Vaccine 33 : 85 91. [CrossRef]
39. Ancelet LR,, Aldwell FE,, Rich FJ,, Kirman JR . 2012. Oral vaccination with lipid-formulated BCG induces a long-lived, multifunctional CD4(+) T cell memory immune response. PLoS One 7 : e45888.[CrossRef]
40. White AD,, Sarfas C,, West K,, Sibley LS,, Wareham AS,, Clark S,, Dennis MJ,, Williams A,, Marsh PD,, Sharpe SA . 2015. Evaluation of the immunogenicity of Mycobacterium bovis BCG delivered by aerosol to the lungs of macaques. Clin Vaccine Immunol 22 : 992 1003. [CrossRef] [PubMed]
41. Soares AP,, Kwong Chung CK,, Choice T,, Hughes EJ,, Jacobs G,, van Rensburg EJ,, Khomba G,, de Kock M,, Lerumo L,, Makhethe L,, Maneli MH,, Pienaar B,, Smit E,, Tena-Coki NG,, van Wyk L,, Boom WH,, Kaplan G,, Scriba TJ,, Hanekom WA . 2013. Longitudinal changes in CD4(+) T-cell memory responses induced by BCG vaccination of newborns. J Infect Dis 207 : 1084 1094. [CrossRef]
42. Tena-Coki NG,, Scriba TJ,, Peteni N,, Eley B,, Wilkinson RJ,, Andersen P,, Hanekom WA,, Kampmann B . 2010. CD4 and CD8 T-cell responses to mycobacterial antigens in African children. Am J Respir Crit Care Med 182 : 120 129. [CrossRef] [PubMed]
43. Andersen P,, Smedegaard B . 2000. CD4(+) T-cell subsets that mediate immunological memory to Mycobacterium tuberculosis infection in mice. Infect Immun 68 : 621 629. [CrossRef]
44. Kipnis A,, Irwin S,, Izzo AA,, Basaraba RJ,, Orme IM . 2005. Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand(hi) population. Infect Immun 73 : 7759 7764. [CrossRef] [PubMed]
45. Ancelet L,, Rich FJ,, Delahunt B,, Kirman JR . 2012. Dissecting memory T cell responses to TB: concerns using adoptive transfer into immunodeficient mice. Tuberculosis (Edinb) 92 : 422 433. [CrossRef]
46. Wherry EJ,, Teichgräber V,, Becker TC,, Masopust D,, Kaech SM,, Antia R,, von Andrian UH,, Ahmed R . 2003. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 4 : 225 234. [CrossRef] [PubMed]
47. Orme IM . 2010. The Achilles heel of BCG. Tuberculosis (Edinb) 90 : 329 332. [CrossRef] [PubMed]
48. Lindenstrøm T,, Knudsen NP,, Agger EM,, Andersen P . 2013. Control of chronic mycobacterium tuberculosis infection by CD4 KLRG1- IL-2-secreting central memory cells. J Immunol 190 : 6311 6319. [CrossRef]
49. Henao-Tamayo MI,, Ordway DJ,, Irwin SM,, Shang S,, Shanley C,, Orme IM . 2010. Phenotypic definition of effector and memory T-lymphocyte subsets in mice chronically infected with Mycobacterium tuberculosis . Clin Vaccine Immunol 17 : 618 625. [CrossRef]
50. Gebhardt T,, Wakim LM,, Eidsmo L,, Reading PC,, Heath WR,, Carbone FR . 2009. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol 10 : 524 530. [CrossRef]
51. Glennie ND,, Yeramilli VA,, Beiting DP,, Volk SW,, Weaver CT,, Scott P . 2015. Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection. J Exp Med 212 : 1405 1414. [CrossRef]
52. Teijaro JR,, Turner D,, Pham Q,, Wherry EJ,, Lefrançois L,, Farber DL . 2011. Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Immunol 187 : 5510 5514. [CrossRef]
53. Giri PK,, Verma I,, Khuller GK . 2006. Protective efficacy of intranasal vaccination with Mycobacterium bovis BCG against airway Mycobacterium tuberculosis challenge in mice. J Infect 53 : 350 356. [CrossRef]
54. Derrick SC,, Kolibab K,, Yang A,, Morris SL . 2014. Intranasal administration of Mycobacterium bovis BCG induces superior protection against aerosol infection with Mycobacterium tuberculosis in mice. Clin Vaccine Immunol 21 : 1443 1451. [CrossRef]
55. Barclay WR,, Busey WM,, Dalgard DW,, Good RC,, Janicki BW,, Kasik JE,, Ribi E,, Ulrich CE,, Wolinsky E . 1973. Protection of monkeys against airborne tuberculosis by aerosol vaccination with bacillus Calmette-Guerin. Am Rev Respir Dis 107 : 351 358.[PubMed]
56. Connor LM,, Harvie MC,, Rich FJ,, Quinn KM,, Brinkmann V,, Le Gros G,, Kirman JR . 2010. A key role for lung-resident memory lymphocytes in protective immune responses after BCG vaccination. Eur J Immunol 40 : 2482 2492. [CrossRef] [PubMed]
57. Sakai S,, Kauffman KD,, Schenkel JM,, McBerry CC,, Mayer-Barber KD,, Masopust D,, Barber DL . 2014. Cutting edge: control of Mycobacterium tuberculosis infection by a subset of lung parenchyma-homing CD4 T cells. J Immunol 192 : 2965 2969. [CrossRef]
58. Moguche AO,, Shafiani S,, Clemons C,, Larson RP,, Dinh C,, Higdon LE,, Cambier CJ,, Sissons JR,, Gallegos AM,, Fink PJ,, Urdahl KB . 2015. ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis. J Exp Med 212 : 715 728. [CrossRef]
59. Gattinoni L,, Lugli E,, Ji Y,, Pos Z,, Paulos CM,, Quigley MF,, Almeida JR,, Gostick E,, Yu Z,, Carpenito C,, Wang E,, Douek DC,, Price DA,, June CH,, Marincola FM,, Roederer M,, Restifo NP . 2011. A human memory T cell subset with stem cell-like properties. Nat Med 17 : 1290 1297. [CrossRef] [PubMed]
60. Stemberger C,, Neuenhahn M,, Gebhardt FE,, Schiemann M,, Buchholz VR,, Busch DH . 2009. Stem cell-like plasticity of naïve and distinct memory CD8+ T cell subsets. Semin Immunol 21 : 62 68. [CrossRef] [PubMed]
61. Gattinoni L,, Zhong XS,, Palmer DC,, Ji Y,, Hinrichs CS,, Yu Z,, Wrzesinski C,, Boni A,, Cassard L,, Garvin LM,, Paulos CM,, Muranski P,, Restifo NP . 2009. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat Med 15 : 808 813. [CrossRef] [PubMed]
62. Graef P,, Buchholz VR,, Stemberger C,, Flossdorf M,, Henkel L,, Schiemann M,, Drexler I,, Höfer T,, Riddell SR,, Busch DH . 2014. Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells. Immunity 41 : 116 126. [CrossRef]
63. Pompei L,, Jang S,, Zamlynny B,, Ravikumar S,, McBride A,, Hickman SP,, Salgame P . 2007. Disparity in IL-12 release in dendritic cells and macrophages in response to Mycobacterium tuberculosis is due to use of distinct TLRs. J Immunol 178 : 5192 5199. [CrossRef] [PubMed]
64. Wu CY,, Kirman JR,, Rotte MJ,, Davey DF,, Perfetto SP,, Rhee EG,, Freidag BL,, Hill BJ,, Douek DC,, Seder RA . 2002. Distinct lineages of T(H)1 cells have differential capacities for memory cell generation in vivo. Nat Immunol 3 : 852 858. [CrossRef]
65. Harrington LE,, Janowski KM,, Oliver JR,, Zajac AJ,, Weaver CT . 2008. Memory CD4 T cells emerge from effector T-cell progenitors. Nature 452 : 356 360. [CrossRef] [PubMed]
66. Leveton C,, Barnass S,, Champion B,, Lucas S,, De Souza B,, Nicol M,, Banerjee D,, Rook G . 1989. T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis . Infect Immun 57 : 390 395.[PubMed]
67. Flory CM,, Hubbard RD,, Collins FM . 1992. Effects of in vivo T lymphocyte subset depletion on mycobacterial infections in mice. J Leukoc Biol 51 : 225 229.[PubMed]
68. Müller I,, Cobbold SP,, Waldmann H,, Kaufmann SH . 1987. Impaired resistance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells. Infect Immun 55 : 2037 2041.[PubMed]
69. Cooper AM,, Dalton DK,, Stewart TA,, Griffin JP,, Russell DG,, Orme IM . 1993. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178 : 2243 2247. [CrossRef] [PubMed]
70. Jouanguy E,, Altare F,, Lamhamedi S,, Revy P,, Emile JF,, Newport M,, Levin M,, Blanche S,, Seboun E,, Fischer A,, Casanova JL . 1996. Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guérin infection. N Engl J Med 335 : 1956 1961. [CrossRef]
71. Jouanguy E,, Lamhamedi-Cherradi S,, Altare F,, Fondanèche MC,, Tuerlinckx D,, Blanche S,, Emile JF,, Gaillard JL,, Schreiber R,, Levin M,, Fischer A,, Hivroz C,, Casanova JL . 1997. Partial interferon-gamma receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guérin infection and a sibling with clinical tuberculosis. J Clin Invest 100 : 2658 2664. [CrossRef]
72. Green AM,, Difazio R,, Flynn JL . 2013. IFN-γ from CD4 T cells is essential for host survival and enhances CD8 T cell function during Mycobacterium tuberculosis infection. J Immunol 190 : 270 277. [CrossRef]
73. Leal IS,, Smedegård B,, Andersen P,, Appelberg R . 2001. Failure to induce enhanced protection against tuberculosis by increasing T-cell-dependent interferon-gamma generation. Immunology 104 : 157 161. [CrossRef]
74. Mittrücker HW,, Steinhoff U,, Köhler A,, Krause M,, Lazar D,, Mex P,, Miekley D,, Kaufmann SH . 2007. Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis. Proc Natl Acad Sci USA 104 : 12434 12439. [CrossRef]
75. Elias D,, Akuffo H,, Britton S . 2005. PPD induced in vitro interferon gamma production is not a reliable correlate of protection against Mycobacterium tuberculosis . Trans R Soc Trop Med Hyg 99 : 363 368. [CrossRef] [PubMed]
76. Majlessi L,, Simsova M,, Jarvis Z,, Brodin P,, Rojas MJ,, Bauche C,, Nouzé C,, Ladant D,, Cole ST,, Sebo P,, Leclerc C . 2006. An increase in antimycobacterial Th1-cell responses by prime-boost protocols of immunization does not enhance protection against tuberculosis. Infect Immun 74 : 2128 2137. [CrossRef]
77. Kagina BM,, Abel B,, Scriba TJ,, Hughes EJ,, Keyser A,, Soares A,, Gamieldien H,, Sidibana M,, Hatherill M,, Gelderbloem S,, Mahomed H,, Hawkridge A,, Hussey G,, Kaplan G,, Hanekom WA ; other members of the South African Tuberculosis Vaccine Initiative . 2010. Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette-Guérin vaccination of newborns. Am J Respir Crit Care Med 182 : 1073 1079. [CrossRef]
78. Cowley SC,, Elkins KL . 2003. CD4+ T cells mediate IFN-gamma-independent control of Mycobacterium tuberculosis infection both in vitro and in vivo. J Immunol 171 : 4689 4699. [CrossRef] [PubMed]
79. Scriba TJ,, Tameris M,, Mansoor N,, Smit E,, van der Merwe L,, Isaacs F,, Keyser A,, Moyo S,, Brittain N,, Lawrie A,, Gelderbloem S,, Veldsman A,, Hatherill M,, Hawkridge A,, Hill AV,, Hussey GD,, Mahomed H,, McShane H,, Hanekom WA . 2010. Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells. Eur J Immunol 40 : 279 290. [CrossRef]
80. Hawkridge T,, Scriba TJ,, Gelderbloem S,, Smit E,, Tameris M,, Moyo S,, Lang T,, Veldsman A,, Hatherill M,, Merwe L,, Fletcher HA,, Mahomed H,, Hill AV,, Hanekom WA,, Hussey GD,, McShane H . 2008. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis 198 : 544 552. [CrossRef] [PubMed]
81. Darrah PA,, Bolton DL,, Lackner AA,, Kaushal D,, Aye PP,, Mehra S,, Blanchard JL,, Didier PJ,, Roy CJ,, Rao SS,, Hokey DA,, Scanga CA,, Sizemore DR,, Sadoff JC,, Roederer M,, Seder RA . 2014. Aerosol vaccination with AERAS-402 elicits robust cellular immune responses in the lungs of rhesus macaques but fails to protect against high-dose Mycobacterium tuberculosis challenge. J Immunol 193 : 1799 1811. [CrossRef]
82. Peng MY,, Wang ZH,, Yao CY,, Jiang LN,, Jin QL,, Wang J,, Li BQ . 2008. Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis. Cell Mol Immunol 5 : 203 208. [CrossRef]
83. Lockhart E,, Green AM,, Flynn JL . 2006. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol 177 : 4662 4669. [CrossRef]
84. Bettelli E,, Carrier Y,, Gao W,, Korn T,, Strom TB,, Oukka M,, Weiner HL,, Kuchroo VK . 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441 : 235 238. [CrossRef]
85. Yang XO,, Pappu BP,, Nurieva R,, Akimzhanov A,, Kang HS,, Chung Y,, Ma L,, Shah B,, Panopoulos AD,, Schluns KS,, Watowich SS,, Tian Q,, Jetten AM,, Dong C . 2008. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28 : 29 39. [CrossRef] [PubMed]
86. Rouvier E,, Luciani MF,, Mattéi MG,, Denizot F,, Golstein P . 1993. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 150 : 5445 5456.[PubMed]
87. Ye P,, Rodriguez FH,, Kanaly S,, Stocking KL,, Schurr J,, Schwarzenberger P,, Oliver P,, Huang W,, Zhang P,, Zhang J,, Shellito JE,, Bagby GJ,, Nelson S,, Charrier K,, Peschon JJ,, Kolls JK . 2001. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med 194 : 519 527. [CrossRef]
88. Guglani L,, Khader SA . 2010. Th17 cytokines in mucosal immunity and inflammation. Curr Opin HIV AIDS 5 : 120 127. [CrossRef] [PubMed]
89. Cruz A,, Fraga AG,, Fountain JJ,, Rangel-Moreno J,, Torrado E,, Saraiva M,, Pereira DR,, Randall TD,, Pedrosa J,, Cooper AM,, Castro AG . 2010. Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis . J Exp Med 207 : 1609 1616. [CrossRef]
90. Griffiths KL,, Stylianou E,, Poyntz HC,, Betts GJ,, Fletcher HA,, McShane H . 2013. Cholera toxin enhances vaccine-induced protection against Mycobacterium tuberculosis challenge in mice. PLoS One 8 : e78312. [CrossRef]
91. Aagaard C,, Hoang T,, Dietrich J,, Cardona PJ,, Izzo A,, Dolganov G,, Schoolnik GK,, Cassidy JP,, Billeskov R,, Andersen P . 2011. A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 17 : 189 194. [CrossRef]
92. Desel C,, Dorhoi A,, Bandermann S,, Grode L,, Eisele B,, Kaufmann SH . 2011. Recombinant BCG ΔureC hly+ induces superior protection over parental BCG by stimulating a balanced combination of type 1 and type 17 cytokine responses. J Infect Dis 204 : 1573 1584. [CrossRef]
93. Acosta-Rodriguez EV,, Rivino L,, Geginat J,, Jarrossay D,, Gattorno M,, Lanzavecchia A,, Sallusto F,, Napolitani G . 2007. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8 : 639 646. [CrossRef]
94. Marín ND,, París SC,, Rojas M,, García LF . 2012. Reduced frequency of memory T cells and increased Th17 responses in patients with active tuberculosis. Clin Vaccine Immunol 19 : 1667 1676. [CrossRef]
95. Nunnari G,, Pinzone MR,, Vancheri C,, Palermo F,, Cacopardo B . 2013. Interferon-γ and interleukin-17 production from PPD-stimulated PBMCss of patients with pulmonary tuberculosis. Clin Invest Med 36 : E64 E71.[PubMed]
96. Perreau M,, Rozot V,, Welles HC,, Belluti-Enders F,, Vigano S,, Maillard M,, Dorta G,, Mazza-Stalder J,, Bart PA,, Roger T,, Calandra T,, Nicod L,, Harari A . 2013. Lack of Mycobacterium tuberculosis-specific interleukin-17A-producing CD4+ T cells in active disease. Eur J Immunol 43 : 939 948. [CrossRef]
97. Loxton AG,, Black GF,, Stanley K,, Walzl G . 2012. Heparin-binding hemagglutinin induces IFN-γ(+) IL-2(+) IL-17(+) multifunctional CD4(+) T cells during latent but not active tuberculosis disease. Clin Vaccine Immunol 19 : 746 751. [CrossRef]
98. Kumar NP,, Anuradha R,, Suresh R,, Ganesh R,, Shankar J,, Kumaraswami V,, Nutman TB,, Babu S . 2011. Suppressed type 1, type 2, and type 17 cytokine responses in active tuberculosis in children. Clin Vaccine Immunol 18 : 1856 1864. [CrossRef] [PubMed]
99. Chen X,, Zhang M,, Liao M,, Graner MW,, Wu C,, Yang Q,, Liu H,, Zhou B . 2010. Reduced Th17 response in patients with tuberculosis correlates with IL-6R expression on CD4+ T Cells. Am J Respir Crit Care Med 181 : 734 742. [CrossRef] [PubMed]
100. Sutherland JS,, Adetifa IM,, Hill PC,, Adegbola RA,, Ota MO . 2009. Pattern and diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease. Eur J Immunol 39 : 723 729. [CrossRef]
101. Scriba TJ,, Kalsdorf B,, Abrahams DA,, Isaacs F,, Hofmeister J,, Black G,, Hassan HY,, Wilkinson RJ,, Walzl G,, Gelderbloem SJ,, Mahomed H,, Hussey GD,, Hanekom WA . 2008. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180 : 1962 1970. [CrossRef]
102. Matthews K,, Wilkinson KA,, Kalsdorf B,, Roberts T,, Diacon A,, Walzl G,, Wolske J,, Ntsekhe M,, Syed F,, Russell J,, Mayosi BM,, Dawson R,, Dheda K,, Wilkinson RJ,, Hanekom WA,, Scriba TJ . 2011. Predominance of interleukin-22 over interleukin-17 at the site of disease in human tuberculosis. Tuberculosis (Edinb) 91 : 587 593. [CrossRef]
103. Khader SA,, Bell GK,, Pearl JE,, Fountain JJ,, Rangel-Moreno J,, Cilley GE,, Shen F,, Eaton SM,, Gaffen SL,, Swain SL,, Locksley RM,, Haynes L,, Randall TD,, Cooper AM . 2007. IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8 : 369 377. [CrossRef]
104. Lalor MK,, Floyd S,, Gorak-Stolinska P,, Ben-Smith A,, Weir RE,, Smith SG,, Newport MJ,, Blitz R,, Mvula H,, Branson K,, McGrath N,, Crampin AC,, Fine PE,, Dockrell HM . 2011. BCG vaccination induces different cytokine profiles following infant BCG vaccination in the UK and Malawi. J Infect Dis 204 : 1075 1085. [CrossRef]
105. Smith SG,, Lalor MK,, Gorak-Stolinska P,, Blitz R,, Beveridge NE,, Worth A,, McShane H,, Dockrell HM . 2010. Mycobacterium tuberculosis PPD-induced immune biomarkers measurable in vitro following BCG vaccination of UK adolescents by multiplex bead array and intracellular cytokine staining. BMC Immunol 11 : 35. [CrossRef]
106. Kassa D,, Ran L,, Geberemeskel W,, Tebeje M,, Alemu A,, Selase A,, Tegbaru B,, Franken KL,, Friggen AH,, van Meijgaarden KE,, Ottenhoff TH,, Wolday D,, Messele T,, van Baarle D . 2012. Analysis of immune responses against a wide range of Mycobacterium tuberculosis antigens in patients with active pulmonary tuberculosis. Clin Vaccine Immunol 19 : 1907 1915. [CrossRef]
107. Basile JI,, Geffner LJ,, Romero MM,, Balboa L,, Sabio Y García C,, Ritacco V,, García A,, Cuffré M,, Abbate E,, López B,, Barrera L,, Ambroggi M,, Alemán M,, Sasiain MC,, de la Barrera SS . 2011. Outbreaks of mycobacterium tuberculosis MDR strains induce high IL-17 T-cell response inpatients with MDR tuberculosis that is closely associated with high antigen load. J Infect Dis 204 : 1054 1064. [CrossRef]
108. Gopal R,, Monin L,, Slight S,, Uche U,, Blanchard E,, Fallert Junecko BA,, Ramos-Payan R,, Stallings CL,, Reinhart TA,, Kolls JK,, Kaushal D,, Nagarajan U,, Rangel-Moreno J,, Khader SA . 2014. Unexpected role for IL-17 in protective immunity against hypervirulent Mycobacterium tuberculosis HN878 infection. PLoS Pathog 10 : e1004099.[CrossRef]
109. Khader SA,, Pearl JE,, Sakamoto K,, Gilmartin L,, Bell GK,, Jelley-Gibbs DM,, Ghilardi N,, deSauvage F,, Cooper AM . 2005. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol 175 : 788 795. [CrossRef]
110. Cooper AM,, Khader SA . 2008. The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev 226 : 191 204. [CrossRef]
111. Gopal R,, Rangel-Moreno J,, Slight S,, Lin Y,, Nawar HF,, Fallert Junecko BA,, Reinhart TA,, Kolls J,, Randall TD,, Connell TD,, Khader SA . 2013. Interleukin-17-dependent CXCL13 mediates mucosal vaccine-induced immunity against tuberculosis. Mucosal Immunol 6 : 972 984. [CrossRef]
112. Wozniak TM,, Saunders BM,, Ryan AA,, Britton WJ . 2010. Mycobacterium bovis BCG-specific Th17 cells confer partial protection against Mycobacterium tuberculosis infection in the absence of gamma interferon. Infect Immun 78 : 4187 4194. [CrossRef]
113. Werninghaus K,, Babiak A,, Gross O,, Hölscher C,, Dietrich H,, Agger EM,, Mages J,, Mocsai A,, Schoenen H,, Finger K,, Nimmerjahn F,, Brown GD,, Kirschning C,, Heit A,, Andersen P,, Wagner H,, Ruland J,, Lang R . 2009. Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation. J Exp Med 206 : 89 97. [CrossRef]
114. Lindenstrøm T,, Woodworth J,, Dietrich J,, Aagaard C,, Andersen P,, Agger EM . 2012. Vaccine-induced th17 cells are maintained long-term postvaccination as a distinct and phenotypically stable memory subset. Infect Immun 80 : 3533 3544. [CrossRef]
115. Orr MT,, Beebe EA,, Hudson TE,, Argilla D,, Huang PW,, Reese VA,, Fox CB,, Reed SG,, Coler RN . 2015. Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy. Vaccine 33 : 6570 6578. [CrossRef]
116. Stenger S,, Hanson DA,, Teitelbaum R,, Dewan P,, Niazi KR,, Froelich CJ,, Ganz T,, Thoma-Uszynski S,, Melián A,, Bogdan C,, Porcelli SA,, Bloom BR,, Krensky AM,, Modlin RL . 1998. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282 : 121 125. [CrossRef]
117. Lu CC,, Wu TS,, Hsu YJ,, Chang CJ,, Lin CS,, Chia JH,, Wu TL,, Huang TT,, Martel J,, Ojcius DM,, Young JD,, Lai HC . 2014. NK cells kill mycobacteria directly by releasing perforin and granulysin. J Leukoc Biol 96 : 1119 1129. [CrossRef]
118. Tzelepis F,, Verway M,, Daoud J,, Gillard J,, Hassani-Ardakani K,, Dunn J,, Downey J,, Gentile ME,, Jaworska J,, Sanchez AM,, Nédélec Y,, Vali H,, Tabrizian M,, Kristof AS,, King IL,, Barreiro LB,, Divangahi M . 2015. Annexin1 regulates DC efferocytosis and cross-presentation during Mycobacterium tuberculosis infection. J Clin Invest 125 : 752 768. [CrossRef]
119. Harriff MJ,, Purdy GE,, Lewinsohn DM . 2012. Escape from the phagosome: the explanation for MHC-I processing of mycobacterial antigens? Front Immunol 3 : 40.[CrossRef] [PubMed]
120. Leavy O . 2011. Antigen presentation: cross-dress to impress. Nat Rev Immunol 11 : 302 303. [CrossRef] [PubMed]
121. Behar SM,, Baehrecke EH . 2015. Tuberculosis: autophagy is not the answer. Nature 528 : 482 483. [CrossRef] [PubMed]
122. Silva CL,, Bonato VL,, Lima VM,, Faccioli LH,, Leão SC . 1999. Characterization of the memory/activated T cells that mediate the long-lived host response against tuberculosis after bacillus Calmette-Guérin or DNA vaccination. Immunology 97 : 573 581. [CrossRef]
123. Wang J,, Santosuosso M,, Ngai P,, Zganiacz A,, Xing Z . 2004. Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. J Immunol 173 : 4590 4597. [CrossRef]
124. Jeyanathan M,, Mu J,, McCormick S,, Damjanovic D,, Small CL,, Shaler CR,, Kugathasan K,, Xing Z . 2010. Murine airway luminal antituberculosis memory CD8 T cells by mucosal immunization are maintained via antigen-driven in situ proliferation, independent of peripheral T cell recruitment. Am J Respir Crit Care Med 181 : 862 872. [CrossRef]
125. Kamath A,, Woodworth JS,, Behar SM . 2006. Antigen-specific CD8+ T cells and the development of central memory during Mycobacterium tuberculosis infection. J Immunol 177 : 6361 6369. [CrossRef]
126. Serbina NV,, Flynn JL . 2001. CD8(+) T cells participate in the memory immune response to Mycobacterium tuberculosis . Infect Immun 69 : 4320 4328. [CrossRef]
127. Carpenter SM,, Nunes-Alves C,, Booty MG,, Way SS,, Behar SM . 2016. A higher activation threshold of memory CD8+ T cells has a fitness cost that is modified by TCR affinity during tuberculosis. PLoS Pathog 12 : e1005380.[CrossRef]
128. Hess J,, Miko D,, Catic A,, Lehmensiek V,, Russell DG,, Kaufmann SH . 1998. Mycobacterium bovis Bacille Calmette-Guérin strains secreting listeriolysin of Listeria monocytogenes . Proc Natl Acad Sci USA 95 : 5299 5304. [CrossRef]
129. Sun R,, Skeiky YA,, Izzo A,, Dheenadhayalan V,, Imam Z,, Penn E,, Stagliano K,, Haddock S,, Mueller S,, Fulkerson J,, Scanga C,, Grover A,, Derrick SC,, Morris S,, Hone DM,, Horwitz MA,, Kaufmann SH,, Sadoff JC . 2009. Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis . Vaccine 27 : 4412 4423. [CrossRef]
130. Derrick SC,, Repique C,, Snoy P,, Yang AL,, Morris S . 2004. Immunization with a DNA vaccine cocktail protects mice lacking CD4 cells against an aerogenic infection with Mycobacterium tuberculosis . Infect Immun 72 : 1685 1692. [CrossRef]
131. Coppel S,, Youmans GP . 1969. Specificity of acquired resistance produced by immunization with mycobacterial cells and mycobacterial fractions. J Bacteriol 97 : 114 120.[PubMed]
132. Smrkovski LL,, Larson CL . 1977. Effect of treatment with BCG on the course of visceral leishmaniasis in BALB/c mice. Infect Immun 16 : 249 257.[PubMed]
133. Ghadirian E,, Kongshavn PA . 1986. Protection of mice against intestinal amoebiasis with BCG, Corynebacterium parvum and Listeria monocytogenes . Parasite Immunol 8 : 663 667. [CrossRef]
134. de Castro MJ,, Pardo-Seco J,, Martinón-Torres F . 2015. Nonspecific (heterologous) protection of neonatal BCG vaccination against hospitalization due to respiratory infection and sepsis. Clin Infect Dis 60 : 1611 1619. [CrossRef]
135. Jensen KJ,, Larsen N,, Biering-Sørensen S,, Andersen A,, Eriksen HB,, Monteiro I,, Hougaard D,, Aaby P,, Netea MG,, Flanagan KL,, Benn CS . 2015. Heterologous immunological effects of early BCG vaccination in low-birth-weight infants in Guinea-Bissau: a randomized-controlled trial. J Infect Dis 211 : 956 967. [CrossRef]
136. Ritz N,, Mui M,, Balloch A,, Curtis N . 2013. Non-specific effect of Bacille Calmette-Guérin vaccine on the immune response to routine immunisations. Vaccine 31 : 3098 3103. [CrossRef]
137. Netea MG,, Quintin J,, van der Meer JW . 2011. Trained immunity: a memory for innate host defense. Cell Host Microbe 9 : 355 361. [CrossRef]
138. Kleinnijenhuis J,, Quintin J,, Preijers F,, Joosten LA,, Ifrim DC,, Saeed S,, Jacobs C,, van Loenhout J,, de Jong D,, Stunnenberg HG,, Xavier RJ,, van der Meer JW,, van Crevel R,, Netea MG . 2012. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci USA 109 : 17537 17542. [CrossRef]
139. Kleinnijenhuis J,, Quintin J,, Preijers F,, Benn CS,, Joosten LA,, Jacobs C,, van Loenhout J,, Xavier RJ,, Aaby P,, van der Meer JW,, van Crevel R,, Netea MG . 2014. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun 6 : 152 158. [CrossRef] [PubMed]
140. Sun JC,, Beilke JN,, Lanier LL . 2009. Adaptive immune features of natural killer cells. Nature 457 : 557 561. [CrossRef] [PubMed]
141. Fu X,, Liu Y,, Li L,, Li Q,, Qiao D,, Wang H,, Lao S,, Fan Y,, Wu C . 2011. Human natural killer cells expressing the memory-associated marker CD45RO from tuberculous pleurisy respond more strongly and rapidly than CD45RO- natural killer cells following stimulation with interleukin-12. Immunology 134 : 41 49. [CrossRef]
142. Davids V,, Hanekom WA,, Mansoor N,, Gamieldien H,, Gelderbloem SJ,, Hawkridge A,, Hussey GD,, Hughes EJ,, Soler J,, Murray RA,, Ress SR,, Kaplan G . 2006. The effect of bacille Calmette-Guérin vaccine strain and route of administration on induced immune responses in vaccinated infants. J Infect Dis 193 : 531 536. [CrossRef]
143. Fine PE . 1995. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346 : 1339 1345. [CrossRef]
144. Aronson NE,, Santosham M,, Comstock GW,, Howard RS,, Moulton LH,, Rhoades ER,, Harrison LH . 2004. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: a 60-year follow-up study. JAMA 291 : 2086 2091. [CrossRef]
145. Barreto ML,, Rodrigues LC,, Cunha SS,, Pereira S,, Hijjar MA,, Ichihara MY,, de Brito SC,, Dourado I . 2002. Design of the Brazilian BCG-REVAC trial against tuberculosis: a large, simple randomized community trial to evaluate the impact on tuberculosis of BCG revaccination at school age. Control Clin Trials 23 : 540 553. [CrossRef]
146. Abubakar I,, Pimpin L,, Ariti C,, Beynon R,, Mangtani P,, Sterne JA,, Fine PE,, Smith PG,, Lipman M,, Elliman D,, Watson JM,, Drumright LN,, Whiting PF,, Vynnycky E,, Rodrigues LC . 2013. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis. Health Technol Assess 17 : 1 372, v–vi.[CrossRef]
147. Tameris M,, Geldenhuys H,, Luabeya AK,, Smit E,, Hughes JE,, Vermaak S,, Hanekom WA,, Hatherill M,, Mahomed H,, McShane H,, Scriba TJ . 2014. The candidate TB vaccine, MVA85A, induces highly durable Th1 responses. PLoS One 9 : e87340.[CrossRef] [PubMed]
148. Billeskov R,, Christensen JP,, Aagaard C,, Andersen P,, Dietrich J . 2013. Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model. PLoS One 8 : e72185.[CrossRef]
149. van Dissel JT,, Arend SM,, Prins C,, Bang P,, Tingskov PN,, Lingnau K,, Nouta J,, Klein MR,, Rosenkrands I,, Ottenhoff TH,, Kromann I,, Doherty TM,, Andersen P . 2010. Ag85B-ESAT-6 adjuvanted with IC31 promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in naïve human volunteers. Vaccine 28 : 3571 3581. [CrossRef]
150. van Dissel JT,, Joosten SA,, Hoff ST,, Soonawala D,, Prins C,, Hokey DA,, O’Dee DM,, Graves A,, Thierry-Carstensen B,, Andreasen LV,, Ruhwald M,, de Visser AW,, Agger EM,, Ottenhoff TH,, Kromann I,, Andersen P . 2014. A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human. Vaccine 32 : 7098 7107. [CrossRef]
151. Reither K,, Katsoulis L,, Beattie T,, Gardiner N,, Lenz N,, Said K,, Mfinanga E,, Pohl C,, Fielding KL,, Jeffery H,, Kagina BM,, Hughes EJ,, Scriba TJ,, Hanekom WA,, Hoff ST,, Bang P,, Kromann I,, Daubenberger C,, Andersen P,, Churchyard GJ . 2014. Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial. PLoS One 9 : e114602.[CrossRef]
152. Luabeya AK,, Kagina BM,, Tameris MD,, Geldenhuys H,, Hoff ST,, Shi Z,, Kromann I,, Hatherill M,, Mahomed H,, Hanekom WA,, Andersen P,, Scriba TJ,, Schoeman E,, Krohn C,, Day CL,, Africa H,, Makhethe L,, Smit E,, Brown Y,, Suliman S,, Hughes EJ,, Bang P,, Snowden MA,, McClain B,, Hussey GD,, Hussey GD . 2015. First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Vaccine 33 : 4130 4140. [CrossRef]
153. Montoya J,, Solon JA,, Cunanan SR,, Acosta L,, Bollaerts A,, Moris P,, Janssens M,, Jongert E,, Demoitié MA,, Mettens P,, Gatchalian S,, Vinals C,, Cohen J,, Ofori-Anyinam O . 2013. A randomized, controlled dose-finding Phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults. J Clin Immunol 33 : 1360 1375. [CrossRef]
154. World Health Organization . 2015. Global Tuberculosis Report 2015. WHO Press, Geneva, Switzerland.
155. Qaqish A,, Huang D,, Chen CY,, Zhang Z,, Wang R,, Li S,, Yang E,, Lu Y,, Larsen MH,, Jacobs WR Jr,, Qian L,, Frencher J,, Shen L,, Chen ZW . 2017. Adoptive transfer of phosphoantigen-specific γδ T cell subset attenuates Mycobacterium tuberculosis infection in nonhuman primates. J Immunol 198 : 4753 4763.
156. Arts RJ,, Carvalho A,, La Rocca C,, Palma C,, Rodrigues F,, Silvestre R,, Kleinnijenhuis J,, Lachmandas E,, Gonçalves LG,, Belinha A,, Cunha C,, Oosting M,, Joosten LA,, Matarese G,, van Crevel R,, Netea MG . 2016. Immunometabolic pathways in BCG-induced trained immunity. Cell Rep 17 : 2562 2571.

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