Loss of CD47 alters CD8+ T cell activation in vitro and immunodynamics in mice
| Autor: | Pulak R. Nath, Dipasmita Pal-Nath, Sukhbir Kaur, Arunkumar Gangaplara, Thomas J. Meyer, Margaret C Cam, David D. Roberts |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | OncoImmunology, Vol 11, Iss 1 (2022) |
| Druh dokumentu: | article |
| ISSN: | 2162402X 2162-402X |
| DOI: | 10.1080/2162402X.2022.2111909 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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