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Y. P. Sun; Exposure of IRBP-specific CD8 Autoreactive T Cells to Low Doses of Autoantigen Preferentially Activates Functionally Suppressive T Cell Subsets. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2836.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate structure and functional difference between CD4 and CD8 autoreactive T cells induced the uveitogenic peptide.
Purified CD4 and CD8 isolated from B6 mice immunized with an uveitogenic peptide, interphotoreceptor retinoid-binding protein (IRBP) 1-20, were stimulated in vitro with varying doses of immunizing peptide. The activated T cells were determined for cytokine production, expression of Foxp3, and the suppressor activity.
CD4 autoreactive T cells underwent full activation when stimulated with high- or medium- concentrations of immunizing peptide, whereas a high dose of antigenic peptide resulted in only modest activation of CD8 autoreactive T cells. Interestingly, when stimulated by a low dose (<0.1 µg/ml) of antigen or by of a high dose of antigen and a small amount of TGF-ß1, the minimally activated CD8 T cells expressed high level of Foxp3 and gained suppressor function.
Autoantigen alone induces only partial rather than full activation of CD8 autoreactive T cells. Full activation of CD8 autoreactive T cells may requires additional stimulatory signals, including those delivered by cytokines produced by activated CD4 T cells. Partial activation of CD8 autoreactive T cells preferentially induces functionally suppressive T cell subsets.Supported in part by NIH grants EY014-366, EY12974, EY14599 and the grant RG3413A4 from the National Multiple Sclerosis Society.
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