Defects in CD4+ T cell LFA-1 integrin-dependent adhesion and proliferation protect Cd47-/- mice from EAE
(2017) In Journal of Leukocyte Biology 101(2). p.493-505- Abstract
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... (More)
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.
(Less)
- author
- publishing date
- 2017-02-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Autoimmune, Neuroinflammation, T lymphocytes, TCR activation
- in
- Journal of Leukocyte Biology
- volume
- 101
- issue
- 2
- pages
- 493 - 505
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:27965383
- scopus:85011395650
- ISSN
- 0741-5400
- DOI
- 10.1189/jlb.3A1215-546RR
- language
- English
- LU publication?
- no
- id
- c6b65668-2744-492f-8166-2170ba9e7437
- date added to LUP
- 2020-02-02 16:54:45
- date last changed
- 2024-05-29 08:22:58
@article{c6b65668-2744-492f-8166-2170ba9e7437,
abstract = {{<p>CD47 is known to play an important role in CD4<sup>+</sup> T cell homeostasis. We recently reported a reduction in mice deficient in the Cd47 gene (Cd47<sup>-/-</sup>) CD4<sup>+</sup> 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<sup>-/-</sup> mice were resistant to experimental autoimmune encephalomyelitis (EAE) as a result of complete failure in CD4<sup>+</sup> T cell activation after myelin oligodendrocyte glycoprotein peptide 35–55 aa (MOG<sub>35–55</sub>) 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<sup>-/-</sup> in EAE. Thus, we hypothesized that failure of T cell activation involved defects in LFA-1 and VLA-4 integrins. We confirmed that Cd47<sup>-/-</sup> mice were resistant to MOG<sub>35–55</sub>-induced EAE. Our data, however, supported a different mechanism that was not a result of failure of CD4<sup>+</sup> T cell activation. Instead, we found that CD4<sup>+</sup> T cells in MOG<sub>35–55</sub>-immunized Cd47<sup>2/2</sup> 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<sup>-/-</sup> CD4<sup>+</sup> 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<sub>35–55</sub>-induced EAE.</p>}},
author = {{Azcutia, Veronica and Bassil, Ribal and Herter, Jan M. and Engelbertsen, Daniel and Newton, Gail and Autio, Anu and Mayadas, Tanya and Lichtman, Andrew H. and Khoury, Samia J. and Parkos, Charles A. and Elyaman, Wassim and Luscinskas, Francis W.}},
issn = {{0741-5400}},
keywords = {{Autoimmune; Neuroinflammation; T lymphocytes; TCR activation}},
language = {{eng}},
month = {{02}},
number = {{2}},
pages = {{493--505}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Leukocyte Biology}},
title = {{Defects in CD4<sup>+</sup> T cell LFA-1 integrin-dependent adhesion and proliferation protect Cd47<sup>-/-</sup> mice from EAE}},
url = {{http://dx.doi.org/10.1189/jlb.3A1215-546RR}},
doi = {{10.1189/jlb.3A1215-546RR}},
volume = {{101}},
year = {{2017}},
}