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N Ardjomand, N Rogers, JC McAlister, PH Tan, AJ T George, FP Larkin; CD28 and CD154 Pathway Costimulatory Blockade Prolongs Corneal Allograft Survival . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2263.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The costimulatory signals for T lymphocyte activation generated through CD80/86 and CD40 on APCs and their respective T cell surface ligands, CD28 and CD154 (CD40L), are each known to be functionally involved in allograft rejection. The effect of blockade of CD28 and/or CD154-mediated costimulation on mouse corneal allograft survival was investigated. Methods: Wild-type or BALB/c background CD28KO mice received C3H strain donor corneas. Graft recipients were treated with i.p. CTLA4-Ig and/or anti-CD154 (MR1) antibody on days 0, 2, 4 post-surgery. Graft survival was compared in treatment groups. Immunohistochemical examination on graft-infiltrating cells was performed following rejection. Results: Median survival time (MST) in untreated BALB/c recipients was 14d. Treatment with CTLA4-Ig, MR1, or both, extended median graft survival to 21, 25 and 29d respectively. MST was 28d in untreated CD28KO mice and 38d in MR1-treated mice, significantly longer than in wild-type. CTLA4-Ig treatment of CD28KO mice resulted in accelerated rejection (MST 16d). Phenotypes of graft-infiltrating T cells were found to be similar in all groups. Conclusion: Combinations of agents blocking the CD28 and CD154 costimulatory pathways have potential for prevention of rejection in clinical corneal transplantation.
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