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The Memory Immune Response to Tuberculosis

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  • Authors: Joanna R. Kirman1, Marcela I. Henao-Tamayo2, Else Marie Agger3
  • Editors: William R. Jacobs Jr.4, Helen McShane5, Valerie Mizrahi6, Ian M. Orme7
    Affiliations: 1: Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand; 2: Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratory, Colorado State University, Fort Collins, CO 80523; 3: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark; 4: Howard Hughes Medical Institute, Albert Einstein School of Medicine, Bronx, NY 10461; 5: University of Oxford, Oxford OX3 7DQ, United Kingdom; 6: University of Cape Town, Rondebosch 7701, South Africa; 7: Colorado State University, Fort Collins, CO 80523
  • Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0009-2016
  • Received 19 January 2016 Accepted 04 April 2016 Published 16 December 2016
  • Joanna R. Kirman, [email protected]
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  • Abstract:

    Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity. More recently, we have learned that the memory response required for effective control of is much more complex, probably involving several phenotypically different CD4 T cell subsets as well as other cell types that are yet to be defined. Herein, we describe recent insights into memory immunity to TB in the context of both animal models and the human infection. With the increasing amount of data generated from clinical testing of novel TB vaccines, we also summarize recent knowledge of vaccine-induced memory immunity.

  • Citation: Kirman J, Henao-Tamayo M, Agger E. 2016. The Memory Immune Response to Tuberculosis. Microbiol Spectrum 4(6):TBTB2-0009-2016. doi:10.1128/microbiolspec.TBTB2-0009-2016.


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Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity. More recently, we have learned that the memory response required for effective control of is much more complex, probably involving several phenotypically different CD4 T cell subsets as well as other cell types that are yet to be defined. Herein, we describe recent insights into memory immunity to TB in the context of both animal models and the human infection. With the increasing amount of data generated from clinical testing of novel TB vaccines, we also summarize recent knowledge of vaccine-induced memory immunity.

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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.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0009-2016
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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.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0009-2016
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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.

Source: microbiolspec December 2016 vol. 4 no. 6 doi:10.1128/microbiolspec.TBTB2-0009-2016
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