CD47 reduces activation‐induced CD4+ T cell death in MOG peptide‐dependent Experimental Autoimmune Encephalomyelitis

Resumen

CD47 is involved in immune cell recruitment and adaptive immune responses. We have recently reported CD47 plays an important role in CD4 T cell recruitment to sites of inflammation in vivo and in vitro. Here we have examined the role of CD47 in a murine experimental autoimmune encephalomyelitis (EAE) model. Surprisingly, immunization of CD47−/− mice with myelin oligodendrocyte glycoprotein (MOG)35–55 peptide does not induce EAE or CNS inflammation. In contrast, transfer of activated, MOG-specific TCR transgenic WT CD4 T cells caused disease in WT and CD47−/− mice, suggesting a defect in the immune cell activation. Accordingly, eight days post MOG immunization, the number of CD4+ T cells in spleens and draining lymph nodes was significantly reduced in CD47−/− vs WT mice (43 and 30% reduction, respectively). A MOG-dependent proliferation assay using CD4 T cells and dendritic cells revealed the defect lay in CD4 T cells from CD47−/− mice (84% reduction). Unexpectedly, we detected greater CD4 T cell activation by MOG immunization in CD47−/− vs WT mice, however, CD47−/− CD4 T cells showed much greater apoptosis in vivo (Annexin-V and TUNEL staining) and in vitro (2.3 fold increase in Annexin-V/7-AAD staining). Our results suggest that CD47 contributes to CD4 T cell recruitment and resistance to self-peptide activation-induced cell death in this EAE model. This work was supported by NIH P01HL03628 and AHA 11POST7730055.