Unregulated antigen-presenting cell activation by T cells breaks self tolerance.

ABSTRACT: T cells proliferate vigorously following acute depletion of CD4⁺ Foxp3⁺ T regulatory cells [natural Tregs (nTregs)] and also when naive T cells are transferred to syngeneic, nTreg-deficient Rag1^-/- hosts. Here, using mice raised in an antigen-free (AF) environment, we show that proliferation in these two situations is directed to self ligands rather than food or commensal antigens. In both situations, the absence of nTregs elevates B7 expression on host dendritic cells (DCs) and enables a small subset of naive CD4 T cells with high self affinity to respond overtly to host DCs: bidirectional T/DC interaction ensues, leading to progressive DC activation and reciprocal strong proliferation of T cells accompanied by peripheral Treg (pTreg) formati

SUBMITTER: Yi J 

PROVIDER: S-EPMC6338877 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature