Abstract
CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-γ. Whether CD4 T cells act as "helper" cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.
Keywords:
CD4 T cell help; CD4 T cells; CD8 T cells; CTL; T cell exhaustion; immunity; infection; interferon gamma; lung; mycobacterium tuberculosis.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Disease Models, Animal
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / metabolism
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Interferon-gamma / metabolism
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Interleukin-2 / metabolism
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Lung / microbiology
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Lung / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mycobacterium tuberculosis / pathogenicity
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Mycobacterium tuberculosis / physiology
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NK Cell Lectin-Like Receptor Subfamily K / genetics
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NK Cell Lectin-Like Receptor Subfamily K / metabolism
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Signaling Lymphocytic Activation Molecule Family / genetics
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Signaling Lymphocytic Activation Molecule Family / metabolism
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Survival Rate
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Transcriptome
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Tuberculosis / immunology*
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Tuberculosis / mortality
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Tuberculosis / pathology
Substances
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Cd244a protein, mouse
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Histocompatibility Antigens Class II
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Interleukin-2
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Klrk1 protein, mouse
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NK Cell Lectin-Like Receptor Subfamily K
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Signaling Lymphocytic Activation Molecule Family
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Interferon-gamma