Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

Non-hematopoietic lymph node stromal cells shape immunity by inducing WIC-I-dependent deletion of self-reactive CD8(+) T cells and WIC-II-dependent anergy of CD4(+) T cells. Here, we show that WIC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of WIC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4(+) as well as CD8(+) T cells became activated, ultimately resulting in transplant rejection. WIC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.