Role of the Choroidal Gamma Delta T Cells in Response to Retinal Pigment Epithelium Injury

Despite their low abundance in the total T lymphocyte pool, gamma delta T (gdT) cells have potent effects in modulating inflammation and immune responses. We previously reported the presence of choroidal gdT cells in a model of chronic degeneration of the retinal pigment epithelium (RPE). The purposes of the current study were to define the functions of choroidal gdT cells and to explore the mechanisms of their interactions with the RPE. In response to sodium iodate (NaIO3) treatment, gdT cell-deficient mice developed profound RPE and retinal damage at dosage that caused minimal effects in wild type mice, and adoptive transfer of gdT cell prevented the sensitization. Purified choroidal gdT cells showed gene expression profile bearing resemblance to the characteristics of regulatory T cells, and expressed immunosuppressive cytokines such as IL-4 and IL-10. Intravitreal injection of IL-4 and IL-10 suppressed NaIO3-induced RPE toxicity. Furthermore, ex vivo co-culture of gdT cells with RPE explants activated IL-10 production, via an aryl hydrocarbon receptor (AhR)-dependent mechanism. Collectively these novel findings from our studies have revealed important roles of choroid gdT cells in maintaining tissue homeostasis and controlling epithelial and immune cell interactions in the outer retina.