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TGF-ß Inhibits Activation and Uveitogenicity of Primary but Not of Fully Polarized Retinal Antigen-Specific Memory-Effector T Cells

¹From the Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland. ²Present address: Department of Immunology, Holland Laboratory of the American Red Cross, Rockville, Maryland; and ³Duke University School of Medicine, Durham, North Carolina.

PURPOSE. TGF-ß 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-ß on uveitogenic T cells were examined.

METHODS. The effects of TGF-ß 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- 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-ß suppressed B7.1 expression on APCs in cultures of lymph node cells from immunized mice. It also suppressed T-cell proliferation, IFN- 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-ß.

CONCLUSIONS. The results suggest that TGF-ß 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-ß 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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