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 pathobionts 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.