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Daniel Engelbertsen

Assistant researcher

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

Author

  • Veronica Azcutia
  • Ribal Bassil
  • Jan M. Herter
  • Daniel Engelbertsen
  • Gail Newton
  • Anu Autio
  • Tanya Mayadas
  • Andrew H. Lichtman
  • Samia J. Khoury
  • Charles A. Parkos
  • Wassim Elyaman
  • Francis W. Luscinskas

Summary, in English

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 (MOG35–55) 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 MOG35–55-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 MOG35–55-immunized Cd472/2 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 MOG35–55-induced EAE.

Publishing year

2017-02-01

Language

English

Pages

493-505

Publication/Series

Journal of Leukocyte Biology

Volume

101

Issue

2

Document type

Journal article

Publisher

John Wiley and Sons

Keywords

  • Autoimmune
  • Neuroinflammation
  • T lymphocytes
  • TCR activation

Status

Published

ISBN/ISSN/Other

  • ISSN: 0741-5400