Regional Immunity of the Eye

Abstract

This article reviews molecular mechanism of intraocular inflammation in animal models and in humans, and the immunological defence system of the eye with particular attention to ocular pigment epithelium. In experimental autoimmune uveitis (EAU), T lymphocytes, particularly CD4(+) T lymphocytes, play a central role in its immunopathogenic mechanisms. In humans, activated CD4(+) T cells also play a central role in the immunopathogenic mechanisms. This notion is demonstrated in two human diseases: one is Vogt-Koyanagi-Harada disease, and the other is human T-cell leukemia virus type 1 (HTLV-1) uveitis. Activated CD4(+) T cells infiltrating the eye are harmful to vision-related cells and tissues in the eye and cause sight-threatening conditions. However, the eye has regional defence systems to protect itself from these harmful activated T cells. We focus on ocular pigment epithelium (PE) and demonstrate immunoregulatory activity of iris PE and retinal PE. Iris PE suppresses activated CD4(+) T cells by cell-to-cell contact with a crucial role played by B7-2 molecule on iris PE and CTLA4 on T cells. The actual immunosuppressive factor being membrane bound TGF-beta. In contrast, retinal PE suppresses activated CD4(+) T cells by soluble factors, such as soluble TGF-beta and thrombospondin 1. In addition to the direct T-cell suppression by ocular PE, ocular PE has the capacity to promote activated T cells to regulatory T cells and use them as a tool to amplify the immune down regulation in the eye. The molecular mechanisms of generation of T regulatory cells by iris PE and retinal PE is also discussed.