CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-g. 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.

Automated summary

CD4 T cells play a crucial role in immunity to tuberculosis by enhancing CD8 effector functions and preventing exhaustion, promoting the survival of infected mice. Vaccines that elicit both CD4 and CD8 T cells are more likely to be successful in generating protective responses against M. tuberculosis infection.