(Left) In the thymus, bone marrow-derived APCs, such as DCs, and mTECs eliminate
self-reactive CD4 T cells either through the induction of apoptosis during
negative selection or re-direction to the Treg cell lineage.
(Right) In the MLN, activated commensal-specific CD4 T cells are either directed
to the Treg cell lineage by CD103+ DCs or deleted through induction
of apoptosis by MHCII+ ILC3s in a process of “intestinal
selection.” ILC3s induce apoptosis by IL-2 withdrawal, which activates
Nur77 and the proapoptotic factor Bim. Conditional deletion of MHCII on ILC3
(MHCIIΔILC3 mice) prevents deletion and leads to expansion
of commensal-specific CD4 T cells, which results in intestinal inflammation in
the presence of appropriate microbiota.