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In Vitro Activation of CD8 Interphotoreceptor Retinoid-Binding Protein-Specific T Cells Requires not only Antigenic Stimulation but also Exogenous Growth Factors¹

Yong Peng^*, Hui Shao^*, Yan Ke^*, Ping Zhang^*, Jim Xiang, Henry J. Kaplan^* and Deming Sun^2,*

^* Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, KY 40202; and Departments of Microbiology, Immunology, and Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

In a previous study, we demonstrated that immunization with the uveitogenic peptide interphotoreceptor retinoid-binding protein (IRBP) 1–20 induces both CD4 and CD8 uveitogenic T cells in the B6 mouse. In the current study, we determined the role of the CD8 IRBP-specific T cells in the pathogenesis of experimental autoimmune uveitis. We also determined the conditions that facilitated the activation of CD8 autoreactive T cells. Our results showed that the ₂-microglobulin^–/– mouse had a greatly decreased susceptibility to induction of experimental autoimmune uveitis by adoptive transfer of IRBP-specific T cells from B6 mice. We also showed that unlike CD4 autoreactive T cells, activated CD8 autoreactive T cells produced only a limited number and amounts of growth factors. As a result, in the absence of exogenously supplied growth factor(s), CD8 T cell activation and expansion were aborted. However, the growth and expansion of triggered CD8 autoreactive T cells could be supported by various cytokines. In addition to factors produced by activated CD4 autoreactive T cells, factors produced by nonlymphoid cells, such as IL-7 and IL-15, and unidentified factors in the culture supernatants of astrocytes and retinal pigment epithelial cells support the CD8 autoreactive T cells as well. Finally, we showed that, although several cytokines augmented the CD8 T cell response in vitro, different cytokines appeared to act on different CD8 subsets or on different activation/differentiation phases of CD8 autoreactive T cells. As a result, cytokines, such as IL-7, supported the proliferation and survival of CD8 IRBP-specific T cells, while others had only a growth-promoting effect.

This article has been cited by other articles:

				Y. Peng, G. Han, H. Shao, Y. Wang, H. J. Kaplan, and D. Sun Characterization of IL-17+ Interphotoreceptor Retinoid-Binding Protein-Specific T Cells in Experimental Autoimmune Uveitis Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4153 - 4161. [Abstract] [Full Text] [PDF]

				Y. Ke, D. Sun, P. Zhang, G. Jiang, H. J. Kaplan, and H. Shao Suppression of Established Experimental Autoimmune Uveitis by Anti-LFA-1{alpha} Ab Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2667 - 2675. [Abstract] [Full Text] [PDF]

				Y. Peng, H. Shao, Y. Ke, P. Zhang, G. Han, H. J. Kaplan, and D. Sun Minimally Activated CD8 Autoreactive T Cells Specific for IRBP Express a High Level of Foxp3 and Are Functionally Suppressive Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2178 - 2184. [Abstract] [Full Text] [PDF]

				P. Zhang, D. Sun, Y. Ke, H. J. Kaplan, and H. Shao The Net Effect of Costimulatory Blockers Is Dependent on the Subset and Activation Status of the Autoreactive T Cells J. Immunol., January 1, 2007; 178(1): 474 - 479. [Abstract] [Full Text] [PDF]