CD47 promotes peripheral T cell survival by preventing dendritic cell–mediated T cell necroptosis

Conventional dendritic cells (cDCs) are required for peripheral T cell homeostasis in lymphoid organs, but the molecular mechanism underlying this requirement has remained unclear. We here show that T cell–specific CD47-deficient (Cd47?T) mice have a markedly reduced number of T cells in peripheral tissues. Direct interaction of CD47-deficient T cells with cDCs resulted in activation of the latter cells, which in turn induced necroptosis of the former cells. The deficiency and cell death of T cells in Cd47?T mice required expression of CD47 or its receptor SIRPa (signal regulatory protein a) on cDCs. The development of CD4+ T helper cell–dependent contact hypersensitivity and inhibition of tumor growth by cytotoxic CD8+ T cells were both markedly impaired in Cd47?T mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function. Overall design: Comparative gene expression profiling analysis of RNA-seq data for T cells and cDC2s isolated from spleen of Cd47f/f mice and Cd47?T mice.