CD4+ T cell expressed CD80 regulates central nervous system effector function and survival during experimental autoimmune encephalomyelitis

Joseph R. Podojil, Adam P. Kohm, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

CD80 expressed on the surface of APCs provides a positive costimulatory signal to naive CD4+ T cells during activation. Therefore, it was hypothesized that treatment of SJL mice with various forms of anti-CD80 mAb during remission from the acute phase of relapsing experimental autoimmune encephalomyelitis (R-EAE) would ameliorate disease progression. We previously reported that treatment of SJL mice with anti-CD80 Fab during R-EAE remission blocked activation of T cells specific for endogenous myelin epitopes, inhibiting epitope spreading and clinical disease progression; however, treatment with the native form of the same anti-CD80 mAb exacerbated disease progression. The current data show that intact anti-CD80 mAb binds both CNS-infiltrating CD4+ T cells and CD11c+ dendritic cells and that exacerbation of R-EAE directly correlates with increased survival and activity of myelin-specific CD4+ T cells, while the percentage of CD11c+ dendritic cells in the CNS and their APC activity was not altered. In vitro data show that cross-linking CD80 on the surface of CD4 + T cells activated in the presence of Th1-promoting cytokines increases the level of T cell activation, effector function, and survival by directly up-regulating the expression levels of transcripts for T-bet, IFN-γ, and Bcl-xL. These findings indicate a novel regulatory role for CD80-mediated intracellular signals in CD4+ T cells and have important implications for using anti-costimulatory molecule mAb therapy in established autoimmune disease.

Original languageEnglish (US)
Pages (from-to)2948-2958
Number of pages11
JournalJournal of Immunology
Volume177
Issue number5
DOIs
StatePublished - Sep 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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