Chapter 9 : Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818104/9781555811594_Chap09-1.gif /docserver/preview/fulltext/10.1128/9781555818104/9781555811594_Chap09-2.gif


The discovery of γ δ T cells originally occurred as an unexpected result of attempts to identify and clone the T-cell receptor (TCR). This chapter presents evidence that γ δ T cells are required in order to prevent the development of chronic disease, which in turn may be a contributing factor in determining whether a microbial pathogen is eradicated or becomes persistent. At first consideration, the numerous accounts of large numbers of γ δ T cells within the inflammatory lesions associated with autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis and its mouse model, experimental autoimmune encephalitis, would appear to indicate a pathogenic rather than immunoregulatory role for γ δ T cells. However, rather than being an indication of involvement in the pathogenesis of these disorders, it can be said that the presence of γ δ T cells is an attempt to downregulate the extent of inflammation associated with these diseases. It has been suggested, however, that γ δ T cells promote the influx of macrophages into the site of infection, resulting in the generation of granulomas, which are essential for bacterial clearance. This hypothesis is based on the finding that the production of macrophage-specific chemokines, such as macrophage inflammatory protein-1α (MlP-1α), MIP-1β, MIP-2, and methyl-accepting chemotaxis protein 1, is reduced in TCR-δ mice following infection. In other cases, however, the bacteria can be reactivated and cause clinical disease.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

(A) Proposed functions for γδ T cells following infection with intracellular bacteria. (B) Kinetics of the growth of and the expansion of γδ T cells in the spleens of mice following infection. Mice were infected with 2 × 10 CFU of ,and the spleens were harvested on the indicated days. Bacterial numbers were determined by plating dilutions of organ homogenates on Luria-Bertani agar plates. γδ T-cell numbers were determined by flow cytometry. The expansion of Vδ6 and Vδ4 γδ T cells, which are the predominant populations that respond to infection with ,occurs when the bacterial numbers are in decline ( ). MΦmacrophage.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

TCR-δ-/- mice develop necrotic liver abscesses following infection with . Wild-type (A) and TCR-δ-/- (B) mice were infected for 6 days with 2 × 104 CFU of , and liver sections were stained with hematoxylin and eosin. Magnification, × 352.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Proposed modulatory function of γδ T cells during the inflammatory response to infection with intracellular bacteria. According to this model, γδ T cells respond to stimulatory ligands, such as Hsp60, expressed by activated macrophages at the conclusion of an immune response to infection. Activated γδ T cells then acquire cytotoxic activity to kill the macrophage. In the absence of γδ T cells, activated macrophages accumulate in the animal, resulting in tissue necrosis as a result of overproduction of inflammatory mediators.

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Allison, J. P. A.,, and W. L. Havran. 1991. The immunobiology of T cells with invariant γδ antigen receptors. Annu. Rev. Immunol. 9: 679 705.
2. Balaji, K.,, S. K. Schwander,, E. A. Rich,, and W. H. Boom. 1995. Alveolar macrophages as accessory cells for human γδ T cells activated by Mycobacterium tuberculosis. J. Immunol. 154: 5959 5968.
3. Balbi, B.,, M. T. Valle,, S. Oddera,, D. Giunti,, F. Manca,, G. A. Rossi,, and L. Allegra. 1993. T-lymphocytes with γδ + + Vδ2 + + antigen receptors are present in increased proportions in a fraction of patients with tuberculosis or with sarcoidosis. Am. Rev. Respir. Dis. 148: 1685 1691.
4. Barnes, P. E.,, C. L. Grisso,, J. S. Abrams,, H. Band,, T. H. Rea,, and R. L. Modlin. 1992. γδ T lymphocytes in human tuberculosis. J. Infect. Dis. 165: 506 512.
5. Barnes, P. F.,, R. L. Modlin,, and J. J. Ellner,. 1994. T-cell responses andcytokines, p. 417 436. In B. R. Bloom (ed.), Tuberculosis. Pathogenesis, Protection, and Control. ASM Press, Washington, D.C.
6. Barrett, T. R.,, T. F. Gajewski,, D. Danielpour,, E. B. Chang,, K. W. Beagley,, and J. A. Bluestone. 1992. Differential function of intestinal intraepithelial lymphocyte subsets. J. Immunol. 149: 1124 1130.
7. Bekker, L. G.,, G. Maartens,, L. Steyn,, and G. Kaplan. 1998. Selective increase in plasma tumor necrosis factor-alpha and concomitant clinical deterioration after initiating therapy in patients with severe tuberculosis. J. Infect. Dis. 178: 580 584.
8. Belles, C.,, A. Kuhl,, R. Nosheny,, and S. R. Carding. 1999. Plasma membrane expression of heat shock protein 60 in vivo in response to infection. Infect. Immun. 67: 4191 4200.
9. Belles, C.,, A. L. Kuhl,, A. J. Donoghue,, Y. Sano,, R. L. O'Brien,, W. Born,, K. Bottomly,, and S. R. Carding. 1996. Bias in the γδ T cell response to Listeria monocytogenes: Vδ6 + 3 + cells are a major component of the γδ T cell response to Listeria monocytogenes. J. Immunol. 156: 4280 4289.
10. Berg, R.,, and D. Savage. 1975. Immune responses of specific-pathogen-ffee and gnotobiotic mice to antigens o f indigenous and nonindigenous microorganisms. Infect. Immun. 11: 320 329.
11. Boog, C. J.P.,, E. R. deGraefF-Meeder,, M. A. Lucassen,, R. vander Zee,, M. M. Voorhorst-Ogink,, J. S. van Kooten,, H. J. Geuze,, and W. van Eden. 1992. Two monoclonal antibodies generated against human HSP60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J. Exp. Med. 175: 1805 1810.
12. Boom, W. H.,, R. S. Wallis,, and K. A. Chervenak. 1991. Human Mycobacterium tuberculosisreactive CD4 + - T - cell clones: heterogeneity in antigen recognition, cytokine production, and cytotoxicity for mononuclear phagocytes. Infect. Immun. 59: 2737 2743.
13. Boom, W. H.,, K. N. Balaji,, R. Nayak,, K. Tsukaguchi,, and K. A. Chervenak. 1994. Characterization of a 10- to 14-kilodalton protease- sensitive Mycobacterium tuberculosis H37Ra antigen that stimulates human γδ T cells. Infect. Immun. 62: 5511 5518.
14. Boom, W.H.,, K. A. Chervenak,, M. A. Mincek,, and J. J. Ellner. 1992. Role of the mononuclear phagocyte as anantigen-presenting cell for human γδ T cells activated by live Mycobacteriumtuberculosis. Infect. Immun. 60: 3480 3487.
15. Born, W.,, L. Hall,, A. Dallas,, J. Boymel,, T. Shinnick,, D. Young,, P. Brennan,, and R. O'Brien. 1990. Recognition of a peptide antigen by heat shock-reactive γδ T lymphocytes. Science 249: 67 69.
16. Born, W. K.,, P. Happ,, A. Dallas,, C. Reardon,, R. Kubo,, T. Schinnick,, P. Brennan,, and R. L. O'Brien. 1990. Recognition of heat shock proteins and γδ cell function. Immunol. Today 11: 40.
17. Borst, J.,, R. J. van de Griend,, J. W. van Oost-veen,, S.-L. Ang,, C. Melief,, J. G. Seidman,, and R. L. H. Bolhuis. 1987. A T cell-receptor γ/CD3 complex found on cloned functional lymphocytes. Nature 325: 683 688.
18. Brenner, M. B.,, J. McLean,, H. Scheft,, J. Riberdy,, S.-L. Ang,, J. G. Seidman,, P. Devlin,, and M. S. Krangel. 1987. Two forms of the T cell-receptor 7 protein found o n peripheral blood cytotoxic T lymphocytes. Nature 325: 689 694.
19. Bukowski, J. F.,, C. T. Morita,, H. Band,, and M. B. Brenner. 1998. Crucial role of TCR7 chain junctional region in prenyl pyrophosphate antigen recognition by γδ T cells. J. Immunol. 161: 286 293.
20. Carding, S. R.,, W. Allan,, S. Kyes,, A. Hayday,, K. Bottomly,, and P. C. Doherty. 1990. Late dominance of the inflammatory process in murine influenza by γ/δ + + T cells. J. Exp. Med. 172: 1225 1231.
21. Carding, S. R.,, W. Allan,, A. McMickle,, and P. C. Doherty. 1993. Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. J. Exp. Med. 177: 475 482.
22. Carter, P.,, and M. Pollard. 1971. Host responses to normal microbial flora in germfree mice. J. Reticuloendothel. Soc. 9: 580 587.
23. Cerf-Bensussan, N.,, and D. Guy-Grand. 1991. Intestinal intraepithelial lymphocytes. Gastroenterol. Clin. N. Am. 20: 549 576.
24. Chan, J.,, and S. H. E. Kaufinann,. 1994. Immune mechanisms ofprotection, p. 389 416. In B. R. Bloom (ed.), Tuberculosis. Pathogenesis, Protection, and Control. ASM Press, Washington, D.C.
25. Contractor, N. V.,, H. Bassiri,, T. Reya,, A. V. Park,, D. C. Baumgart,, M. Wasik,, S. G. Emerson,, and S. R. Carding. 1998. Lymphoid hyperplasia, autoimmunity and compromised intestinal intraepithelial lymphocyte development in colitis-free gnotobiotic interleukin 2-deficient mice. J. Immunol. 160: 385 394.
26. Cooper, A. M.,, D. K. Dalton,, T. A. Stewart,, J. P. Griffin,, D. G. Russell,, and I. M. Orme. 1993. Disseminated tuberculosis in interferon-y gene-disrupted mice. J. Exp. Med. 178: 2243 2247.
27. Davis, M.M., 1991>. T-cell receptors forantigen, p. 44 61. In B. D. Schwartz (ed.), Immunology. The Upjohn Company, Kalamazoo, Mich.
28. De Libero, G.,, G. Casorati,, C. Giachino,, C. Carbonara,, N. Migone,, P. Matzinger,, and A. Lanzavecchia. 1991. Selection by two powerful antigens may account for the presence of the major population of human peripheral γ/δ T cells. J. Exp. Med. 173: 1311 1318.
29. Dianda, L.,, A. M. Hanby,, N. A. Wright,, A. Sebesteny,, A. C. Hayday,, and M. J. Owen. 1997. T cell receptor-αβ-deficient mice fail to develop colitis in the absence of a microbial environment. Am. J. Pathol. 150: 91 97.
30. DiTirro, J.,, E. R. Rhodes,, A. D. Roberts,, J. M. Burke,, A. Mukasa,, A. M. Cooper,, A. A. Frank,, W. K. Born,, and I. M. Orme. 1998. Disruption of cellular inflammatory response to Listeria monocytogenes infection in mice with disruptions in targeted genes. Infect. Immun. 66: 2284 2289.
31. D'Souza, C. D.,, A. M. Cooper,, A. A. Frank,, R. J. Mazzaccaro,, B. R. Bloom,, and I. M. Orme. 1997. An anti-inflammatory role for γδ T lymphocytes in acquired immunity to Mycobacterium tuberculosis. J. Immunol. 158: 1217 1221.
32. Duchmann, R.,, E. Marker-Hermann,, and K. H. Meyer zum Buschenfelde. 1996. Bacteriaspecific T cell-clones are selective in their reactivity towards different enterobacteria or H. pylori and increased in inflammatory bowel disease. Scand. J. Immunol. 44: 71 79.
33. Duchmann, R.,, I. Kaiser,, E. Hermann,, W. Mayet,, K. Ewe,, and K.-H. MeyerZumBuschenfelde. 1995. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin. Exp. Med. 102: 448 455.
34. Egan, P.,, C. Belles,, and S. R. Carding. 1998. The properties o f γδ T-cells. Biochemist 20: 29 33.
35. Flynn, J. L.,, J. Chan,, K. J. Triebold,, D. K. Dalton,, T. A. Stewart,, and B. R. Bloom. 1993. An essential role for IFN-7 in resistance to Mycobacterium tuberculosis infection. J. Exp. Med. 178: 2249 2254.
36. Flynn, J.L.,, M. A. Goldstein,, K. J. Triebold,, B. Roller,, and B. R. Bloom. 1992. Major histocompatibility complex classI-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 89: 12013 12017.
37. Flynn, J. L.,, M. M. Goldstein,, J. Chan,, K. J. Triebold,, K. Pfeffer,, C. J. Lowenstein,, R. Schreiber,, T. W. Mak,, and B. R. Bloom. 1995. Tumor necrosis factor-α is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2: 561 572.
38. Follows, G. A.,, M. E. Munk,, A. J. Gatrill,, P. Conradt,, and S. H. E. Kaufmann. 1992. Gamma interferon and interleukin-2, but not interleukin-4, are detected in gamma-delta T-cell cultures after activation with bacteria. Infect. Immun. 60: 1229 1231.
39. Fu, Y.-X.,, C. E. Roark,, K. Kelly,, D. Drevets,, P. Campbell,, R. O'Brien,, and W. Born. 1994. Immune protection and control of inflammatory tissue necrosis by γδ T cells. J. Immunol. 153: 3101 3115.
40. Fujihashi, K.,, T. Taguchi,, W. K. Aicher,, J. R. McGhee,, J. A. Bluestone,, J. H. Eldridge,, and H. Kiyono. 1992. Immunoregulatory functions for murine intraepithelial lymphocytes: γδT cell receptor positive (TCR +) T cells abrogate oral tolerance, while αβ TCR + T cells provide B cell help. J. Exp. Med. 175: 695 707.
41. Garside, P.,, and A. M. Mowat. 1997. Mechanisms of oral tolerance. Crit. Rev. Immunol. 17: 119 137.
42. Guy-Grand, D.,, M. Malassis-Seris,, C. Briot-tet,, and P. Vassalli. 1991. Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts and cytoplasmic granules. J. Exp. Med. 173: 1549 1552.
43. Haas, W.,, P. Pereira,, and S. Tonegawa. 1993. Gamma/delta cells. Annu. Rev. Immunol. 11: 637 685.
44. Haregewoin, A.,, G. Soman,, R. C. Horn,, and R. W. Finberg. 1989. Human γδ T cells respond to mycobacterial heat shock protein. Nature 340: 309 311.
45. Harrison, L. C.,, M. Dempsey-Collier,, D. R. Kramer,, and K. Takahashi. 1996. Aerosol insulin induces regulatory CD8 γδ T cells that prevent murine insulin-dependent diabetes. J. Exp. Med. 184: 2167 2174.
46. Hard, F.U.,, J. Martin,, and W. Neupert. 1992. Protein folding in the cell: the role of molecular chaperones Hsp70 and Hsp60. Annu. Rev. Biophys. Biomoi Struct. 21: 293 322.
47. Havlir, D. V.,, J. J. Ellner,, K. A. Chervenak,, and W. H. Boom. 1991. Selective expansion of human γδ T cells by Mycobacterium tuberculosisinfected macrophages. J. Clin. Investig. 87: 729 737.
48. Heilig, J. S.,, and S. Tonegawa. 1986. Diversity of murine gamma genes and expression in fetal and adult lymphocytes. Nature 322: 836.
49. Hein, W. R.,, and C. R. MacKay. 1991. Prominence of γδ T cells in the ruminant immune system. Immunol. Today 12: 30 34.
50. Helgeland, L.,, J. T. Vaage,, B. Rolstad,, T. Midtvedt,, and P. Brandtzaeg. 1996. Microbial colonization influences composition and T cellreceptor V p repertoire of intraepithelial lymphocytes in rat intestine. Immunology 89: 494 501.
51. Helgeland, L.,, P. Brandtzaeg,, B. Rolstad,, and J. T. Vaage. 1997. Sequential development of intraepithelial γδ and αβ T lymphocytes expressing CD8αβ in neonatal rat intestine; requirement for the thymus. Immunology 92: 447 456.
52. FQromatsu, K.,, Y. Yoshikai,, G. Matsuzaki,, S. Ohga,, K. Muramori,, K. Matsumoto,, J. A. Bluestone,, and K. Nomoto. 1992. A protective role of γδ T cells in primary infection with Listeria monocytogenes in mice. J. Exp. Med. 175: 49 56.
53. Hou, S.,, P. C. D. J. Katz,, and S. R. Carding. 1992. Extent of γδ T cell involvement in the pneumonia caused by Sendai virus. Cell. Immunol. 143: 183 188.
54. Hsieh, B.,, M. D. Schrenzel,, T. Mulvania,, H. D. Lepper,, L. Di Molfetto-Landon,, and D . A. Ferrick. 1996. In vivo cytokine production in murine listeriosis: evidence for immunoregulation by γδ + T cells. J. Immunol. 156: 232 237.
55. Huang, S.,, W. Hendricks,, A. Althage,, S. Hemmi,, H. Bluethmann,, R. Kamijo,, J. Vilcek,, R. M. Zinkernagel,, and M. Aguet. 1993. Immune responses in mice that lack the interferon- gamma receptor. Science 259: 1742 1745.
56. Ito, M.,, N. Kojiro,, T. Ikeda,, T. Ito,, J. Funada,, and T. Kokubu. 1992. Increased proportions of peripheral blood γδ T cells in patients with pulmonary tuberculosis. Chest 102: 195 199.
57. Janeway, C. A. J.,, and P. Travers. 1997. Immunobiology. The Immune System in Health and Disease, 3rd ed. Garland Publishing Inc., New York, N.Y.
58. Janeway, C. A. J.,, B. Jones,, and A. C. Hayday. 1988. Specificity and function of T cells bearing γδ receptors. Immunol. Today 9: 73 76.
59. Kabelitz, D.,, A. Bender,, T. Prospero,, S. Wesselborg,, O. Janssen,, and K. Pechold. 1991. The primary response of human γδ T cells to Mycobacterium tuberculosis is restricted to Vγ9-bearingcells. J. Exp. Med. 173: 1331 1337.
60. Kabelitz, D.,, A. Bender,, S. Schondelmaier,, B. Schoel,, and S. H. E. Kaufmann. 1990. A large fraction of human peripheral blood γδ + T cells is activated by Mycobacterium tuberculosis but not by its 65-kDa heat shock protein. J. Exp. Med. 171: 667 674.
61. Ke, Y.,, K. Pearce,, J. P. Lake,, H. K. Ziegler,, and J. A. Kapp. 1997. γδT lymphocytes regulate the induction and maintenance of oral tolerance. J. Immunol. 158: 3610 3618.
62. Komano, H.,, Y. Fujiura,, M. Kawaguchi,, S. Matsumoto,, Y. Hashimoto,, S. Obana,, P. Mombaerts,, S. Tonegawa,, H. Yamamoto,, S. Itohara,, M. Nanno,, and H. Ishikawa. 1995. Homeostatic regulation of intestinal epithelia by intraepithelial γδ T cells. Proc. Natl. Acad. Sci. USA 92: 6147 6151.
63. Kumaratne, D. S.,, A. S. Pitkie,, P. Drysdale,, J. S. H. Gaston,, R. Kiessling,, P. B. Iles,, C. J. Ellis,, J. Innes,, and R. Wise. 1990. Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis. Clin. Exp. Immunol. 80: 314 323.
64. Lanier, L. L.,, J. J. Ruitenberg,, and J. H. Phillips. 1986. C D 3 + T lymphocytes that express neither CD4 nor CD8 antigens. J. Exp. Med. 164: 339 344.
65. Lefrancois, L. 1991. Phenotypic complexity of intraepithelial lymphocytes of the small intestine. Immunol. Today 147: 1746 1750.
66. Lefrancois, L.,, and T. Goodman. 1989. In vivo modulation of cytolytic activity and Thy-1 expression in TCR-γδ + intraepithelial lymphocytes. Science 243: 1716 1718.
67. Li, B.,, H. Bassiri,, M. D. Rossman,, P. Kramer,, A. F.-S. Eyuboglu,, M. Torres,, E. Sada,, T. Imir,, and S. R. Carding. 1998. Involvement of Fas/Fas-ligand pathway in activation-induced cell death of mycobacteria-reactive human γδ T cells: a mechanism for the loss of γδ T cells in patients with pulmonary tuberculosis. J. Immunol. 161: 1558 1567.
68. Li, B.,, M. D. Rossman,, T. Imir,, A. F. Oner- Eyuboglu,, C. W. Lee,, R. Biancaniello,, and S. R. Carding. 1996. Disease-specific changes in γδ T cell repertoire and function in patients with pulmonary tuberculosis. J. Immunol. 157: 4222 4229.
69. Li, H.,, M. I. Lebedeva,, A. S. Llera,, B. A. Fields,, M. B. Brenner,, and R. A. Mariuzza. 1998. Structure of the Vδ domain of a human γδ T cell antigen receptor. Nature 391: 502 506.
70. Lorgat, F.,, M. M. Keraan,, P. T. Lukey,, and S. R. Rees. 1992. Evidence for in vivo generation of cytotoxic T cells: PPD-stimulated lymphocytes from tuberculous pleural effusions demonstrate enhanced cytotoxicity with accelerated kinetics of induction. Am. Rev. Respir. Dis. 145: 418 423.
71. Machado, C. S. M.,, M. A. M. Rodrigues,, and H. V. L. Maffei. 1994. Gut intraepithelial lymphocyte counts in neonates, infants and children. Acta Pediatr. 83: 1264 1267.
72. McMenamin, C.,, C. Pimm,, M. McKersey,, and P. G. Holt. 1994. Modulation of IgE responsesto inhaled antigen in mice by antigenspecific γδ T cells. Science 265: 1869 1871.
73. McVay, L. D.,, S. S. Jaswal,, C. Kennedy,, A. Hayday,, and S. R. Carding. 1998. The generation of human γδ T cell repertoires during fetal development. J. Immunol. 160: 5851 5860.
74. Mengel, J.,, F. Cardillo,, L. S. Aroeira,, O. Williams,, M. Russo,, and N. M. Vaz. 1995. Antiy γδ T cell antibody blocks the induction of oral tolerance to ovalbumin in mice. Immunol. Lett. 48: 97 100.
75. Mombaerts, P.,, J. Arnoldi,, F. Russ,, S. Tonegawa,, and S. H. E. Kaufmann. 1993. Different roles ofαβ and γδ T cells in immunity against an intracellular bacterial pathogen. Nature 365: 53 56.
76. Moore, W.,, and L. Hodeman. 1975. Discussion of current bacteriologic investigations of the relationship between intestinal flora, diet and colon cancer. Cancer Res. 35: 3418 3420.
77. Moreau, M.,, D. Ducuzeau,, D. Guy-Grand,, and M. Muller. 1978. Increase in the population of duodenal immunoglobulin A plasmocytes in axenic mice associated with different living or dead bacterial strains of intestinal origin. Infect. Immun. 21: 532 539.
78. Morita, C. T.,, H. K. Lee,, D. S. Leslie,, Y. Tanaka,, J. F. Bukowski,, and E. Marker-Hermann. 1999. Recognition of nonpeptide prenyl pyrophosphate antigens by human γδ T cells. Microbes Infect. 1: 175 186.
79. Morita, C. T.,, E. M. Beckman,, J. F. Bukowski,, Y. Tanaka,, H. Band,, B. R. Bloom,, D . E. Golan,, and M. B. Brenner. 1995. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human γδ T cells. Immunity 3: 495 507.
80. Mosely, R. L.,, D. Styre,, and J. R. Klein. 1990. Differentiation and functional maturation of bone marrow derived intestinal epithelial T cells expressing membrane T cell receptor in athymic radiation chimeras. J. Immunol. 145: 1369 1375.
81. Munk, M. E.,, A. J. Gatrill,, and S. H. E. Kaufmann. 1991. In vitro activation of human y 8 T cells by bacteria: evidence for specific interleukin secretion and target cell lysis. Curr. Top. Microbiol. Immunol. 173: 159 165.
82. Munk, M. E.,, B. Schoel,, S. Modrow,, R. W. Karr,, R. A. Young,, and S. H. E. Kaufmann. 1989. T lymphocytes from healthy individuals with specificity to self-epitopes shared by mycobacterial and human 65-kilodalton heat shock protein. J. Immunol. 143: 2844 2850.
83. O'Brien, R. L.,, Y.-X. Fu,, R. Cranfill,, A. Dallas,, C. Ellis,, C. Reardon,, J. Lang,, S. R. Carding,, R. Kubo,, and W. Born. 1992. Heat shock protein Hsp60-reactive γδ cells: a large, diversified T-lymphocyte subset with highly focused specificity. Proc. Natl. Acad. Sci. USA 89: 4348 4352.
84. Ohga, S.,, Y. Yoshikai,, Y. Takeda,, K. Muramori,, and K. Nomoto. 1990. Sequential appearance of γδ and αβ-bearing T cells in the peritoneal cavity during i.p infection with Listeria monocytogenes. Eur. J. Immunol. 20: 533 540.
85. Panchamoorthy, G.,, J. McLean,, R. L. Modlin,, C. T. Morita,, S. Ishikawa,, M. B. Brenner,, and H. Band. 1991. A predominance of the T cell receptor Vγ2/Vγδ2 subset in human mycobacteria- responsive T cells suggests germline gene encoded recognition. J. Immunol. 147: 3360 3366.
86. Peach, S.,, M. Lock,, D. Katz,, I. Todd,, and S. Tabaqchali. 1978. Mucosal-associated bacterial flora of the intestine in patients with Crohn's disease and in a control group. Gut 19: 1034 1042.
87. PefTer, K.,, B. Schoel,, H. Guile,, S. H. E. Kaufmann,, and H. Wanger. 1990. Primary responses of human T cells to mycobacteria: a frequent set o f γδ T cells are stimulated by proteaseresistant ligands. Eur. J. Immunol. 20: 1175 1184.
88. Peng, S. L.,, M. P. Madaio,, A. C. Hayday,, and J. Craft. 1996. Propagation and regulation of systemic autoimmunity by γδ T cells. J. Immunol. 157: 5689 5698.
89. Pirzer, U.,, A. Schonhaar,, B. Fleischer,, E. Hermann,, K. Hermann,, and K. H. Meyer zum Buschenfelde. 1991. Reactivity of infiltrating T lymphocytes with microbial antigens in Crohn's disease. Lancet 338: 1238 1239.
90. Pollard, M.,, and N. Sharon. 1970. Response of the Peyer's patches in germfree mice to antigenic stimulation. Infect. Immun. 2: 96 100.
91. Poussier, P.,, P. Edouard,, C. Lee,, M. Binnie,, and M. Julius. 1992. Thymus-independent development and negative selection of T cells expressing T cell receptor α/β in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes. J. Exp. Med. 176: 187 199.
92. Raviglione, M.C.,, D. E. Snider,, and A. Kochi. 1995. Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic. JAMA 273: 220 226.
93. Roberts, S. J.,, A. L. Smith,, A. B. West,, L. Wen,, R. C. Findly,, M. J. Owen,, and A. C. Hayday. 1996. T-cell αβ and γδ + deficient mice display abnormal but distinct phenotypes towards a natural, widespread infection of the intestinal epithelium. Proc. Natl. Acad. Sci. USA 93: 11774 11779.
94. Rock, E. P.,, P. R. Sibbald,, M. M. Davis,, and Y. - H. Chien. 1994. CDR3 length in antigenspecific immune receptors. J. Exp. Med. 179: 323 328.
95. Rook, G. A. W.,, J. Taverne,, C. Leveton,, and J. Steele. 1987. The role of gamma-interferon, vitamin D 3 metabolites and tumour necrosis factor in the pathogenesis o f tuberculosis. Immunology 62: 229 234.
96. Sarawar, S.,, S. R. Carding,, W. Allan,, A. McMickle,, K. Fujihashi,, H. Kiyono,, J. R. McGhee,, and P. C. Doherty. 1993. Cytokine profiles in bronchoalveolar lavage cells from mice with influenza pneumonia: consequences of CD4 + and CD8 + T cell depletion. Reg. Immunol. 5: 142 150.
97. Schild, H.,, N. Matvaddat,, C. Litzenberger,, E. W. Ehrich,, M. M. Davis,, J. A. Bluestone,, L. Matis,, R. K. Draper,, and Y. Chien. 1994. The nature of major histocompatibility complex recognition by γδ T cells. Cell 76: 29 37.
98. Schluger, N. W.,, and W. N. Rom. 1998. The host immune response to tuberculosis. Am. J. Respir. Crit. Care Med. 157: 679 691.
99. Selwyn, P.,, D. Hartel,, V. A. Lewis,, E. E. Schoenbaum,, S. H. Vermund,, R. S. Klein,, A. T. Walker,, and G. H. Friedland. 1989. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N. Engl. J. Med. 320: 545 549.
100. Shroff, K.,, K. Meslin,, and J. J. Cebra. 1995. Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanendy colonizing the gut. Infect. Immun. 63: 3904 3913.
101. Skeen, M. J.,, and H. K. Ziegler. 1993. Induction of murine peritoneal γ/δ T cells and their role in resistance to bacterial infection. J. Exp. Med. 178: 971 984.
102. Soltys, B. J.,, and R. S. Gupta. 1996. Immunoelectron microscopic localization of the 60- kDa heat shock chaperonin protein (Hsp60) in mammalian cells. Exp. Cell Res. 222: 16 27.
103. Stenger, S.,, D. A. Hanson,, R. Teitelbaum,, P. Dewan,, K. R. Niazi,, C. J. Froelich,, T. Ganz,, S. Thoma-Uszynski,, A. Melian,, C. Bogdan,, S. A. Porcelli,, B. R. Bloom,, A. M. Krensky,, and R. L. Modlin. 1998. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282: 121 125.
104. Suzuki, H.,, G. S. Duncan,, H. Takimoto,, and T. W. Mak. 1997. Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL2-receptor p chain. J. Exp. Med. 185: 499 505 .
105. Taurog, J. D.,, J. A. Richardson,, J. T. Croft,, W. A. Simmons,, M. Zhou,, J. L. Fernandez- Sueiro,, E. Balish,, and R. E. Hammer. 1994. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J. Exp. Med. 180: 2359 2364.
106. Tazi, A.,, F. Bouchonnet,, D. Valeyre,, J. Cadranel,, J. P. Battesti,, and A. J. Hance. 1992. Characterization of γδ T lymphocytes in the peripheral blood of patients with active tuberculosis. Am. Rev. Respir. Dis. 146: 1216 1220.
107. Tazi, A.,, I. Fajac,, D. Soler,, D. Valeyre,, J. P. Battesti,, and A. J. Hance. 1991. Gamma/delta T-lymphocytes are not increased in number in granulomatous lesions of patients with tuberculosis and sarcoidosis. Am. Rev. Respir. Dis. 144: 1373 1376.
108. Ueta, C.,, I. Tsuyuguchi,, H. Kawasumi,, T. Takashima,, H. Toba,, and S. Kishimoto. 1994. Increase in γδ T cells in hospital workers who are in close contact with tuberculosis patients. Infect. Immun. 62: 5434 5440.
109. Umesaki, Y.,, Y. Okada,, S. Matsumoto,, A. Imaoka,, and H. Setoyama. 1995. Segmented filamentous bacteria are indigenous intestinal bacteria that activate intraepithelial lymphocytes and induce M H C class II molecules and fucosyl asialo GM1 glycolipids on the small intestinal epithelial cells in the ex-germfree mouse. Immunology 39: 555 562.
110. Unanue, E. R. 1997. Studies in listeriosis show the strong symbiosis between the innate and cellular system and the T cell response. Immunol. Rev. 158: 11 25.
111. Unanue, E. R. 1997. Why listeriosis? A perspective on cellular immunity to infection. Immunol. Rev. 158: 5 9.
112. Viitanen, P. V.,, A. A. Gatenby,, and G. H. Lorimer. 1992. Purified chaperonin 60 (groEL) interacts with the normative states o f a multitude of Escherichia coli proteins. Protein Sci. 1: 363 369.
113. Viney, J.L.,, P. J. Kilshaw,, and T. T. MacDonald. 1990. Cytotoxic α/β + and γ/δ + T cells in the murine intestinal epithelium. Eur. J. Immunol. 20: 1623 1626.
114. 113a.World Health Organization. 1998. Fact sheet no. 19. World Health Organization, Geneva, Switzerland.
114. Yamamoto, S.,, F. Russ,, H. C. Teixeira,, P. Conradt,, and S. H. E. Kaufmann. 1993. Listeria monocytogenes-mduced gamma interferon secretion by intestinal intraepithelial γδ T lymphocytes. Infect. Immun. 61: 2154 2161.
115. Zeilstra-Ryalls, J.,, O. Fayet,, and C. Georgopoulos 1991. The universally conserved GroE(Hsp60) chaperonins. Annu. Rev. Microbiol. 45: 301 325.


Generic image for table

Contrasting features and properties of y8 T cells and other lymphocyte lineages

Citation: Egan P, Carding S. 2000. Influence of γδ T Cells on the Development of Chronic Disease and Persistent Bacterial Infections, p 165-182. In Nataro J, Blaser M, Cunningham-Rundles S (ed), Persistent Bacterial Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818104.ch9

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error