CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection [preprint]
Lu, Yu-Jung ; Barreira-Silva, Palmira ; Boyce, Shayla ; Powers, Jennifer ; Cavallo, Kelly ; Behar, Samuel M
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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.
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bioRxiv 2021.02.23.432461; doi: https://doi.org/10.1101/2021.02.23.432461. Link to preprint on bioRxiv.
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This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
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Now published in Cell Reports doi: 10.1016/j.celrep.2021.109696