OncoImmunology (Dec 2022)

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

  • Pulak R. Nath,
  • Dipasmita Pal-Nath,
  • Sukhbir Kaur,
  • Arunkumar Gangaplara,
  • Thomas J. Meyer,
  • Margaret C Cam,
  • David D. Roberts

DOI
https://doi.org/10.1080/2162402X.2022.2111909
Journal volume & issue
Vol. 11, no. 1

Abstract

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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 in vitro and in vivo 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 in vitro, short-term stimuli elevated pathogen-reactive gene expression and enhanced proliferation and the effector phenotypes of Cd47-deficient relative to Cd47-sufficient CD8+ T cells. In contrast, persistent TCR stimulation limited the effector phenotypes of Cd47−/− CD8+ T cells and enhanced their apoptosis signature. CD8+ T cell expansion and activation in vivo induced by acute lymphocytic choriomeningitis virus (LCMV) infection did not differ in the absence of CD47. However, the frequency and effector phenotypes of Cd47−/− 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.

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