CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis.

Abstract

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 (<i>Cd47</i>^ΔT) 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 <i>Cd47</i>^ΔT mice required expression of its receptor signal regulatory protein α 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 <i>Cd47</i>^ΔT mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.