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G. Jiang; Relative Efficiency of Retinal Astrocytes and Retinal Pigmental Epithelium (RPE) in Autoreactive Uveitogenic T Cell Re-Stimulation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2632.
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© ARVO (1962-2015); The Authors (2016-present)
Re-activation of autoreactive T cells in the target organ is one of the critical events of pathogenesis of uveitis. In this study, we have compared the efficiency of two parenchymal cells in the eye, retinal astrocytes and RPE, in uveitogenic T cell re-stimulation.
Proliferation of uveitogenic T cells derived from experimental autoimmune uveitis (EAU) susceptible mice (B10RIII) and Th1 and Th17 cytokine production were assessed in the presence of retinal astrocytes, RPE as well as APCs derived from syngeneic spleen.
Non-activated or activated astrocytes are as efficient as peripheral APCs in inducing IRBP161-180 T cell proliferation, IL-2 secretion and differentiation into pro-inflammatory T cells. However, RPE are much less potent than astrocytes in presenting uveitogenic peptide to IRBP-specific T cells, indicating inefficient Ag processing. The capacity of astrocytes to re-stimulate uveitogenic T cells requires B7-2 and ICOSL molecules, whereas CD28-B7.1 interaction contributes to T cell activation by APCs from periphery. Furthermore, astrocytes are able to induce both Th1 and Th17 cells, but only maintain Th17 but not Th1 cytokine production.
The hierarchy of APC established in this study indicates that retinal astrocytes are the most efficient in the re-stimulation of uveitogenic T cells, suggesting that astrocytes from EAU susceptible mice may effectively contribute to Th1 responses leading to ocular inflammation and tissue damage. These potentially pathogenic responses could be counteracted by RPE cells.
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