Defects in CD4+ T cell LFA-1 integrin-dependent adhesion and proliferation protect Cd47−/− mice from EAE

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Mayadas, Tanya¹  Parkos, Charles A.¹  Engelbertsen, Daniel¹  Bassil, Ribal⁴  Lichtman, Andrew H.⁵  Elyaman, Wassim⁵  Newton, Gail⁵  Khoury, Samia J.⁷  Autio, Anu⁷  Herter, Jan M.⁷  Luscinskas, Francis W.⁷ 

[1] and;..Abou Haidar Neuroscience Institute, American University of Beirut, Lebanon;Ann Romney Center for Neurologic Diseases, Brigham and Women’Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women’Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA;s Hospital and Harvard Medical School, Boston, Massachusetts, USA

关键词: neuroinflammation;    autoimmune;    TCR activation;    T lymphocytes;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CD47 is known to play an important role in CD4⁺ T cell homeostasis. We recently reported a reduction in mice deficient in the Cd47 gene (Cd47^−/−) CD4⁺ T cell adhesion and transendothelial migration (TEM) in vivo and in vitro as a result of impaired expression of high-affinity forms of LFA-1 and VLA-4 integrins. A prior study concluded that Cd47^−/− mice were resistant to experimental autoimmune encephalomyelitis (EAE) as a result of complete failure in CD4⁺ T cell activation after myelin oligodendrocyte glycoprotein peptide 35–55 aa (MOG_35–55) immunization. As the prior EAE study was published before our report, authors could not have accounted for defects in T cell integrin function as a mechanism to protect Cd47^−/− in EAE. Thus, we hypothesized that failure of T cell activation involved defects in LFA-1 and VLA-4 integrins. We confirmed that Cd47^−/− mice were resistant to MOG_35–55-induced EAE. Our data, however, supported a different mechanism that was not a result of failure of CD4⁺ T cell activation. Instead, we found that CD4⁺ T cells in MOG_35–55-immunized Cd47^−/− mice were activated, but clonal expansion contracted within 72 h after immunization. We used TCR crosslinking and mitogen activation in vitro to investigate the underlying mechanism. We found that naïve Cd47^−/− CD4⁺ T cells exhibited a premature block in proliferation and survival because of impaired activation of LFA-1, despite effective TCR-induced activation. These results identify CD47 as an important regulator of LFA-1 and VLA-4 integrin-adhesive functions in T cell proliferation, as well as recruitment, and clarify the roles played by CD47 in MOG_35–55-induced EAE.

【 授权许可】

CC BY