IL-10 and natural regulatory T cells: two independent anti inflammatory mechanisms in HSV induced ocular immonopathology (B63)

Abstract

Abstract Our past studies have shown a protective role for both CD4+CD25+Foxp3+ natural regulatory T cells (nTregs) as well as IL-10 in Herpes Simplex Virus (HSV) induced Stromal Keratitis (SK). Among several other mechanisms, IL-10 has been shown to be involved in the nTreg mediated suppression. We have shown in vitro that blocking of IL-10 could partially block the Treg mediated suppression of activated effectors isolated from SK lesions. But it is not known whether in the in vivo conditions, IL-10 and nTreg influence the SK pathology independently or in concert. Interestingly, IL-10−/− animals depleted of nTregs prior to ocular HSV infection had more severe SK lesion as compared to undepleted IL-10−/− animals. These results show the presence of two independent anti inflammatory mechanisms in SK. Along this line, by using mice expressing GFP-Foxp3 we could not show CD4+GFP-Foxp3+IL-10+ cells in the DLNs and spleens of infected wild-type (WT) mice although animals depleted of nTregs had higher levels of IL-10 in the DLNs post infection. Furthermore, by using WT, IL-10−/− and nTreg depleted WT and IL-10−/− animals we have compared the relative importance of IL-10 and nTregs in reducing SK pathology. Although disease severity was significantly higher in IL-10−/− and both the nTreg depleted groups as compared to WT, highest severity was found in the IL-10−/− mice depleted of nTregs. Intracellular cytokine staining with UV-HSV and polyclonal stimulation of the cells isolated from infected corneas, DLN and spleens revealed that IL-10 has more profound anti inflammatory effects in SK as compared to nTregs and that the later could act in an IL-10 independent manner.