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D. Sun, Y. Peng, P. Zhang, Y. Ke, H.J. Kaplan, H. Shao; CD8 Autoreactive T Cells Specific for Interphotoreceptor Retinoid–Bingding Protein (IRBP) Can Be, but Only Minimally, Activated in the Absence of CD4 T Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1780.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the role of CD8–IRBP–specific T cells in the pathogenesis of EAU and determine the conditions that lead to the activation of CD8–IRBP–specific autoreactive T cells.
EAU was induced in B6 and B6–ß2m–/– mice by adoptive transfer of T cells specific for IRBP 1–20. The purified CD4+ and CD8+ T cells were stimulated by immunizing IRBP 1–20 and APC in the absence or presence of cytokines (IL2, IL4, IL7, IL12, IL15, IL21, IFN–αß), and the proliferation of T cells and cytokine production were assessed. Antigen–specific CD8 cells were determined by binding to IRBP peptide–complexed with recombinant MHC class I (H–2Kb) dimmers. In vitro survival of the CD8 cell was determined by flow cytometry analysis. Finally, CFSE–labeled IRBP–specific T cells were injected to recipient mice, and the survival of the injected T cells assessed at varying days post injection using flow cytometry analysis.
Transfer of T cells from immunized B6 mice to naïve B6 mice repeatedly induced severe uveitis; however, the same number of T cells induced only very mild disease in B6–ß2m–/– mice, which fail to express MHC class I antigen. High doses of Ag induced only weak proliferative response in CD8 T cells. The results of screening of a panel of common cytokines demonstrated that a number of cytokines, including IL2, IL4, IL7 and IL15, had enhancing effects on the Ag–dependent response of CD8+ T cells; whereas the same cytokine did not significantly enhanced CD4 response.
i) Lacking CD8 activity greatly reduced the disease–inducibility of IRBP–specific T cell; ii) Unlike CD4 IRBP–specific T cells, activated CD8 IRBP–specific T cells produced only a limited number and amounts of growth factors. As a result, the growth and expansion of triggered CD8 autoreactive T cells were supported by various cytokines. iii) In addition to factors produced by activated CD4 autoreactive T cells, factors produced by non–lymphoid cells, such as IL–7 and IL–15, and unidentified factors in the culture supernatants of astrocytes and retinal pigment epithelial cells (RPEs) were able to support the activation and expansion of CD8 autoreactive T cells.
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