CD28 costimulation is required for induction of autoimmune, but not for endotoxin-induced, uveitis

P. Silver, K. Hathcock, C. C. Chan, J. M. Green, C. B. Thompson, R. Caspi

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Abstract

Optimal T cell activation requires both the engagement of TCR by Antigen/MHC and of CD28 by B7 molecule(s). The purpose of this study was to investigate if CD28 is essential for induction of immunologically mediated disease in two murine uveitis models: 1) Experimental Autoimmune Uveitis (EAU), a T cell mediated autoimmune disease induced by immunization with retinal antigen (IRBP); and 2) endotoxin-induced uveitis, an ocular inflammatory response elicited by footpad injection of LPS where T cells have been shown to play a role, but whose mechanism is not fully understood. B10.A mice treated with antibodies to B7-1 and B7-2 individually or together were not protected from developing EAU, as indicated by presence of retinal damage equivalent to controls 21 days after immunization. However, CD28-deficient mice were not able to develop disease, and had reduced proliferative responses to IRBP. In contrast, the CD 28-deficient mice were fully capable of developing LPS uveitis 24 h after challenge, as indicated by the number of inflammatory cells and level of IL-6 in the anterior chamber which were equivalent to or greater than those in controls. We conclude that CD28 costimulation is required for EAU induction and for priming of uveitogenic effector T cells. The finding that full-blown EAU developed in normal mice despite anti-B7-1/B7-2 treatment may indicate that other non-B7-1/B7-2 ligands for CD28 may play a role. In contrast, CD28 costimulation is not required for induction of endotoxin uveitis.

Original languageEnglish
Pages (from-to)A1205
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

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    Silver, P., Hathcock, K., Chan, C. C., Green, J. M., Thompson, C. B., & Caspi, R. (1996). CD28 costimulation is required for induction of autoimmune, but not for endotoxin-induced, uveitis. FASEB Journal, 10(6), A1205.