Requirement of B7-mediated costimulation in the induction of experimental autoimmune anterior uveitis

H. Shao, M. D. Woon, S. Nakamura, J. H. Sohn, P. A. Morton, N. S. Bora, H. J. Kaplan

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

PURPOSE. To study the role of costimulatory signaling through the CD28-B7 interaction in experimental autoimmune anterior uveitis (EAAU). METHODS. Naive Lewis rats were immunized with insoluble melanin-associated antigen (MAA) derived from bovine iris and ciliary body. CTLA4-Fc, a recombinant protein comprised of the extracellular domain of human CTLA4 bound to mouse IgG2a Fc, was used to block the CD28-B7 interaction. A mutant version (CTLA4-Fc-mutant) was used as a control. The effect of CTLA4-Fc on the in vivo induction of disease with MAA was studied. Subsequently, the mechanism by which CTLA4-Fc blocked the interaction of CD28 and B7 was investigated in vivo, using the adoptive transfer of T cells derived from CTLA4-Fc-treated rats, and in vitro, using the proliferative response and cytokine production of MAA-T cells in the presence of CTLA4-Fc. RESULTS. CTLA4-Fc markedly reduced the incidence and severity of EAAU in Lewis rats after sensitization with MAA. The adoptive transfer of sensitized T cells from CTLA4-Fc-treated donors did not induce EAAU in naive recipients. CTLA4-Fc inhibited the expansion of antigen-specific MAA-T cells and the production of TNF-α. CONCLUSIONS. The costimulatory signal delivered through CD28-B7 is required for the induction and pathogenesis of EAAU. In the absence of this signal, antigen-specific expansion of MAA reactive T cells as well as production of TNF-α is inhibited. Abrogation of this costimulatory signal may be an important therapeutic option for EAAU.

Original languageEnglish (US)
Pages (from-to)2016-2021
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume42
Issue number9
StatePublished - Aug 20 2001
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Shao, H., Woon, M. D., Nakamura, S., Sohn, J. H., Morton, P. A., Bora, N. S., & Kaplan, H. J. (2001). Requirement of B7-mediated costimulation in the induction of experimental autoimmune anterior uveitis. Investigative Ophthalmology and Visual Science, 42(9), 2016-2021.