Lymph node (LN) stromal cells can express major histocompatibility complex (MHC) class II, but the full relevance of this expression has been unclear. In eLife, Mebius and colleagues use LN transplants to demonstrate a key role for stromal cell MHC class II in the maintenance of peripheral immunological homeostasis. MHC class II–deficient LNs transplanted into wild-type hosts accumulate activated T cells, and such transplants are eventually rejected, presumably due to intense activation of the cells that they are housing. This effect is localized to the transplanted MHC class II–deficient LNs, because endogenous wild-type LNs in the same host are intact. Mechanistically, the expression of MHC class II by LN stroma seems to specifically support the homeostatic proliferation of regulatory T cells via the presentation of antigen. This function seems to be relevant for the maintenance of peripheral tolerance, as LN grafts that express specific antigen can regulate experimental models of delayed-type hypersensitivity responses and rejection of skin grafts.

eLife (19 November 2014) doi:10.7554/eLife.04433