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Feng Lin, Nader Sheibani, Timothy S. Kern, Suber S. Huang, Zhidan Tu; Retinal Pericytes Are Immunosuppressive. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2580.
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Accumulating evidence indicates that the chronic inflammation plays important roles in the pathogenesis of diabetic retinopathy, but how such inflammation is controlled in the retinal capillaries is not clear. Retinal pericytes are critical for retinal vascular integrity which contributes to the blood-retina barrier to maintain the immunoprivileged status of the eye. The loss of the retinal pericytes is a hallmark of early stage diabetic retinopathy. We hypothesize that retinal pericytes are immunosuppressive, therefore the loss of them favors retinal inflammation. In this study, we investigated whether retinal pericytes inhibit immune responses.
Retinal pericytes were isolated from transgenic Immortomice (C57BL/6 background) and characterized. The immunosuppressive potential of the pericytes was assessed by CFSE-based T and B cell proliferation assays. In brief, to determine whether retinal pericytes suppress T cell responses, CFSE-labeled T cells were activated by antigen presenting cells together with anti-CD3 mAbs, and then co-cultured with different numbers of retinal pericytes. After incubation, the T cell proliferation was assessed by measuring CFSE fluorescence dilution using flow cytometry. To determine whether pericytes suppress B cell responses, CFSE-labeled B cells were activated by anti-CD40and IL-4, then co-cultured with different numbers of pericytes. After incubation, the B cell proliferation was assessed by flow cytometry similarly to that in the T cell assays. To determine whether soluble factors and/or cell-cell contact are required for inhibiting T and B cell responses, retinal pericytes cultured in a transwell system were investigated using the same methods described above.
Retinal pericytes are highly immunosuppressive. The isolated retinal pericytes potently inhibit both T and B cell proliferation in a dose-dependent manner. The T and B cell inhibitory activity of retinal pericytes decreases but does not abolish in transwell experiments, indicating that both soluble factors and cell-cell contact are involved in the retinal pericyte-mediated immunosuppression.
These results reveal a new function of retinal pericytes, suggesting that the immunosuppressive activity of the retinal pericytes contributes to ocular immune privilege. This also offers a novel mechanism by which pericyte loss might contribute to the development of diabetic retinopathy.
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