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Hui Xu, Phyllis B. Silver, Teresa K. Tarrant, Chi-Chao Chan, Rachel R. Caspi; TGF-β Inhibits Activation and Uveitogenicity of Primary but Not of Fully Polarized Retinal Antigen-Specific Memory-Effector T Cells. Invest. Ophthalmol. Vis. Sci. 2003;44(11):4805-4812. doi: 10.1167/iovs.02-0843.
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purpose. TGF-β exerts suppressive effects on immunity, but its potential applications in therapy of ocular autoimmunity have not been widely explored. In the present study, the effects of TGF-β on uveitogenic T cells were examined.
methods. The effects of TGF-β on newly primed cells from mice given a uveitogenic regimen of interphotoreceptor retinoid-binding protein (IRBP) were compared with the effects on fully polarized Th1 cells from a long-term uveitogenic T-cell line. The parameters measured were T-cell proliferation, IFN-γ production, induction of IL-12R expression, triggering of pathogenicity, and expression of costimulatory molecules on antigen-presenting cells (APCs) during in vitro exposure to antigen.
results. TGF-β suppressed B7.1 expression on APCs in cultures of lymph node cells from immunized mice. It also suppressed T-cell proliferation, IFN-γ production, IL-12 receptor accumulation, and the IL-12-promoted acquisition of uveitogenic function. In contrast, the polarized Th1 cells were either resistant to suppression or were enhanced by TGF-β.
conclusions. The results suggest that TGF-β suppresses acquisition of effector functions by autopathogenic T cells, in part by interfering with their response to IL-12 through downregulation of IL-12R expression and in part through inhibition of APC function. The data suggest that although TGF-β may effectively inhibit activation and recruitment of new T cells into the effector pool, it may be less effective in suppressing the reactivation of already polarized memory T cells that are less dependent on IL-12 and costimulation.
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