"Th1 environment induces collapse and acquisition of effector phenotype by Foxp3+Treg during lethal intestinal infection"
In the present study, using a model of lethal oral infection with Toxoplasma gondii, we examined the fate of both induced and natural Treg in the face of strong inflammatory responses occurring in a tolerogenic?prone environment. We found that during highly Th1-polarized mucosal immune responses, Treg populations collapse via multiple pathways including blockade of Treg induction and disruption of endogenous Treg homeostasis. In particular, shutdown of IL-2 in the highly Th1-polarized environment triggered by infection directly contributes to Treg incapacity to parallel effector responses and eventually leads to immunopathogenesis. Furthermore, we found that environmental cues provided by both local dendritic cells and effector T cells can superimpose T-bet and IFN-γ expression by Treg. These data reveal a novel mechanism for Th1 pathogenicity that extends beyond their proinflammatory program to limit Treg survival.