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R. D. Megaw, J. Liversidge, R. Barker, J. V. Forrester, S. Hewick; Identification of Regulatory T Cell Epitopes on Retinal S-Antigen. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5127.
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To determine whether there is evidence for S-antigen peptide specific T cell regulatory responses or immune system bias in uveitis patients.
A panel of 79, overlapping 15-mer peptides spanning the whole length of hS-antigen were synthesized and purified. Endogenous posterior uveitis (EPU) patients with well defined clinical uveitis entities and matched controls were recruited and peripheral blood mononuclear cells (PBMC)set up in proliferation assays with the individual peptides under conditions designed to support recall rather than primary T helper cell responses. A sensitive ELISA assay was used to detect cytokines (IL-10 and TGF-ß) in the supernatants.
Chi squared test showed PBMC proliferation in response to peptide stimulation was higher in patients than controls (p=0.014), and patient cells secreted higher levels of IL-10 (p=0.000009), but lower levels of TGF-ß (p=0.026) than controls in response to S-antigen peptides. When individual responses were analysed it was clear that PBMC was significantly higher in patients with active disease compared with those with inactive disease. When individual peptide responses were analysed, peptide 13 elicited IL-10 in the absence of proliferation in 4 patients and 4 controls.
Peptide 13 of S-antigen may represent an immunoregulatory epitope, and merits further investigation. Future studies should focus on new patients with active disease or paients on minimal immunosuppressive therapy, and should include analysis of PBMC for evidence of regulatory T cell activity.
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