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Major Role of T Cells in the Generation of IL-17⁺ Uveitogenic T Cells¹

Yan Cui^*, Hui Shao, Chen Lan, Hong Nian^*, Rebecca L. O'Brien, Willi K. Born, Henry J. Kaplan and Deming Sun^2,*

^* Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033; Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202; and Integrated Department of Immunology, National Jewish Health, Denver, CO 80206

We show that in vitro activation of interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from C57BL/6 mice immunized with an uveitogenic IRBP peptide (IRBP_1–20) under TH17-polarizing conditions is associated with increased expansion of T cells expressing the TCR. We also show that highly purified β or T cells from C57BL/6 mice immunized with IRBP_1–20 produced only small amounts of IL-17 after exposure to the immunizing Ag in vitro, whereas a mixture of the same T cells produced greatly increased amounts of IL-17. IRBP-induced T cells from IRBP-immunized TCR-^–/– mice on the C57BL/6 genetic background produced significantly lower amounts of IL-17 than did wild-type C57BL/6 mice and had significantly decreased experimental autoimmune uveitis-inducing ability. However, reconstitution of the TCR-^–/– mice before immunization with a small number of T cells from IRBP-immunized C57BL/6 mice restored the disease-inducing capability of their IRBP-specific T cells and greatly enhanced the generation of IL-17⁺ T cells in the recipient mice. Our study suggests that T cells are important in the generation and activation of IL-17-producing autoreactive T cells and play a major role in the pathogenesis of experimental autoimmune uveitis.

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 EY014366, EY017373 (to D.S.), EY12974, and EY14599 (to H.S.). D.S. is a recipient of a senior investigator award from Research to Prevent Blindness.

² Address correspondence and reprint requests to Dr. Deming Sun, Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CA 90033. E-mail address: dsun{at}doheny.org

³ Abbreviations used in this paper: EAU, experimental autoimmune uveitis; IRBP, interphotoreceptor retinoid-binding protein; MOG, myelin oligodendrocyte glycoprotein; HSP, heat shock protein.