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The Net Effect of Costimulatory Blockers Is Dependent on the Subset and Activation Status of the Autoreactive T Cells¹

Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202

In this study, we investigated whether CD4 and CD8 autoreactive T cells have different costimulatory requirements for their activation in vitro by testing the effect of a panel of Abs specific for various costimulatory molecules. Our results showed that CD8 interphotoreceptor retinoid-binding protein-specific T cells are more dependent on costimulatory molecules for activation than their CD4 counterparts. Interphotoreceptor retinoid-binding protein-specific T cells are less dependent on costimulatory molecules in the secondary response than the primary response. We also showed that blockade of costimulatory molecules can either promote or inhibit the proliferation of autoreactive T cells, depending on the degree of activation of the cells. Our results show that anti-costimulatory molecule treatment can have diverse actions on autoreactive T cell subsets, the net effect being determined by the subset of immune cells affected and the type and dose of treatment used.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grants NEI EY12974 (to H.S.), EY14599 (to H.S.), and NEI-EY014366 (to D.S.), Vision Research Infrastructure Development (R24 EY015636), Grant RG3413A4 from the National Multiple Sclerosis Society, and the Commonwealth of Kentucky Research Challenge Trust Fund.

² Address correspondence and reprint requests to Dr. Hui Shao, Kentucky Lions Eye Center, Department of Ophthalmology and Vision Sciences, University of Louisville, 301 East Muhammad Ali Boulevard, Louisville, KY 40202. E-mail address: h0shao01{at}louisville.edu

³ Abbreviations used in this paper: EAU, experimental autoimmune uveitis; IRBP, interphotoreceptor retinoid-binding protein.