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H. Keino, S. Masli, B. Turpie, J.W. Streilein; CD8+ Regulatory T Cells of ACAID Express Genes that Inhibit their Effector Functions, while Promoting their Regulatory Functions . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1054.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: CD8+ regulatory T cells of ACAID suppress bystander effector T cells by unknown mechanisms. In order to gain insight into these mechanisms, we sought to identify differentially expressed genes in these cells following exposure to appropriate antigen presenting cells (APC). Methods: Ovalbumin (OVA)-specific CD8+ T cells from OT-I Tcr transgenic mice were exposed to OVA-pulsed, TGF-b2-pretreated (or untreated) APCs. Total RNA was isolated from these cells and used to synthesize cRNA, which was hybridized to MU74Av2 Affymetrix genome microarray chips. Differential gene expression was analyzed using the Resolver bioinformatics analytical software. Results : In regulatory T cells, 106 genes were up-regulated (compared to control cells), including IL-9, MMP-9, TGF-beta, retinoic acid receptor, and CD94. Sixty six genes were down-regulated, including IFNg, IL-12 receptor b1, and granzyme B. Conclusion: Genes up-regulated in CD8+ regulatory T cells of ACAID promote TGFb activation (MMP-9), inhibit effector T cell activation (CD94) while promoting IL-2-dependent proliferation, and are shared with CD4+CD25+ suppressor cells (IL-9). Down-regulated genes suppress activation of T cell effector function (IL-12 Rb1, IFNg, granzyme B). The molecules that mediate suppression may exist among these and other differentially expressed genes.
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