Th19 - Regulation of Antigen Presenting Cells by Retinal Pigment Epithelial Cells

One of the mechanisms of ocular immune privilege is the suppression of phagosome maturation within potential antigen presenting cells. This has implications on the presentation of antigen on MHC class II. The suppression is mediated by soluble immune regulators produced by retinal pigment epithelial cells (RPE). This regulation is diminished under experimental autoimmune uveitis (EAU) conditions but recovers following treatment with the anti-inflammatory neuropeptide α-melanocyte stimulating hormone (α-MSH). To see if there is an effect of RPE on APC activation of T cells, we in vitro treated APC processing antigen with the condition-media of RPE-eyecups from naive, EAU, and α-MSH-treated EAU mouse eyes. These APC were assayed for cytokine production and used in vitro to activate T cells from antigen-immunized mice. The T cells were assayed by ELISA for cytokines and by flow cytometry for changes in CD25 and FoxP3 cell populations. The APC treated with the RPE-eyecup conditioned media had significantly suppressed TNF-α production with induced IL-10 production. The conditioned-media of RPE-eyecup from any mouse eye did not suppress or enhance APC antigen-stimulated T cell production of IFN-γ, IL-17, or IL-10. However, there was suppression in the expansion of CD25⁺FoxP3^- T cells with no change in the CD25⁺FoxP3⁺ Treg cell population. These results suggest that the immune regulation mediated by RPE may not induce Treg cell activity but more about generating an anti-inflammatory environment that minimizes effector T cell expansion. In addition, the results suggest that melanocortin-based therapy works to maintain or return normal immune regulating activity by RPE.