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We recently reported a reduction in mice deficient in the Cd47 gene (Cd47\u2212\/\u2212) 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\u2212\/\u2212 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\u201355 aa (MOG35\u201355) 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\u2212\/\u2212 in EAE. Thus, we hypothesized that failure of T cell activation involved defects in LFA-1 and VLA-4 integrins. We confirmed that Cd47\u2212\/\u2212 mice were resistant to MOG35\u201355-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 MOG35\u201355-immunized Cd47\u2212\/\u2212 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 na\u00efve Cd47\u2212\/\u2212 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 MOG35\u201355-induced EAE.<\/jats:p>","DOI":"10.1189\/jlb.3a1215-546rr","type":"journal-article","created":{"date-parts":[[2016,12,14]],"date-time":"2016-12-14T02:05:22Z","timestamp":1481681122000},"page":"493-505","source":"Crossref","is-referenced-by-count":15,"title":["Defects in CD4+ T cell LFA-1 integrin-dependent adhesion and proliferation protect <i>Cd47<\/i>\u2212\/\u2212 mice from EAE"],"prefix":"10.1093","volume":"101","author":[{"given":"Veronica","family":"Azcutia","sequence":"first","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ribal","family":"Bassil","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan M","family":"Herter","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Engelbertsen","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail","family":"Newton","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anu","family":"Autio","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Mayadas","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew H","family":"Lichtman","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samia J","family":"Khoury","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"},{"name":"Abou Haidar Neuroscience Institute, American University of Beirut , Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles A","family":"Parkos","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wassim","family":"Elyaman","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis W","family":"Luscinskas","sequence":"additional","affiliation":[{"name":"Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,12,13]]},"reference":[{"key":"2023011712051170600_B1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0962-8924(00)01906-1","article-title":"Integrin-associated protein (CD47) and its ligands","volume":"11","author":"Brown","year":"2001","journal-title":"Trends Cell Biol."},{"key":"2023011712051170600_B2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-immunol-032713-120142","article-title":"The interaction between signal regulatory protein alpha (SIRPa) and CD47: structure, function, and therapeutic target","volume":"32","author":"Barclay","year":"2014","journal-title":"Annu. 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