Loss of CD47 alters CD8+ T cell activation and immunodynamics in mice.

CD47 has established roles in the immune system for regulating macrophage phagocytosis and lymphocyte activation, with growing evidence of its cell-intrinsic regulatory roles in natural killer and CD8+ T cells. CD47 limits antigen-dependent cytotoxic activities of human and murine CD8+ T cells, but its role in T cell activation kinetics remains unclear. Using and models, we show here that CD47 differentially regulates CD8+ T cell responses to short- versus long-term activation. Although CD47 was not required for T cell development in mice and early activation , short-term stimuli elevated pathogen-reactive gene expression and enhanced proliferation and the effector phenotypes of deficient relative to sufficient CD8+ T cells. In contrast, persistent TCR stimulation limited the effector phenotypes of CD8+ T cells and enhanced their apoptosis signature. CD8+ T cell expansion and activation induced by acute lymphocytic choriomeningitis virus (LCMV) infection did not differ in the absence of CD47. However, the frequency and effector phenotypes of CD8+ T cells were constrained in chronic LCMV-infected as well as in mice bearing B16 melanoma tumors. Therefore, CD47 regulates CD8+ T cell activation, proliferation, and fitness in a context-dependent manner.