Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (T-reg) cell responses. However, the bacteria that induce effector T (T-eff) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both T-reg cell responses during homeostasis and T-eff cell responses during colitis, as suggested by an increased overlap between the T-eff/T-reg TCR repertoires with colitis. Four of six T-reg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion of luminal Bacteroides species seen during colitis did not trigger a commensurate T-eff cell response. Unlike other T-reg cell-inducing bacteria, Helicobacter species are known patho-bionts and cause disease in immunodeficient mice. Thus, our study suggests a model in which mucosal bacteria elicit context-dependent T-reg or T-eff cell responses to facilitate intestinal tolerance or inflammation.