Comparison of WT vs. MHCII KO CD8 T cell transcriptomes from lungs of Mycobacterium tuberculosis infected mice

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines including interferon-?. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis (Mtb) is unknown. We compared transcriptomes of purified lung CD8 T cells from Mtb infected WT and MHCII KO mice. Using two independent models, we validated RNA-seq results and showed that CD4 T cell help enhanced CD8 effector functions and prevented CD8 T cell exhaustion. We demonstrated synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restricted 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. Overall design: CD8 T cells were purified using anti-CD8 beads from lungs of aerosolized Mtb (strain Erdman) infected WT or MHCII KO mice at 8 weeks post infection. Around 70 Mtb/lung were detected 1 day after infection. Transcriptomes of purified CD8 T cells were analyzed. Replicates were CD8 T cells from indivisual WT or MHCII KO mice.