Immune tolerance and autoimmune uveoretinitis: the role of the ocular microenvironment

Two major self-antigens, S-antigen and interphotoreceptor retinoid-binding protein, which can induce uveoretinitis, exist in the eye. However, immunologic tolerance to these self-antigens is generated and maintained. Two major mechanisms have been demonstrated by which tolerance to tissue-specific self-antigens is maintained. One is central tolerance in the thymus where autoreactive T cells are deleted by medullary thymic epithelial cells expressing the autoimmune regulator gene (Aire) and the other is peripheral tolerance mediated by regulatory T cells such as Foxp3(+)CD25(+)CD4(+) T cells. In addition, the eye is an immune privileged site where indigenous immunomodulatory mechanisms allow immune protection of the eye in a manner that is largely devoid of immunogenic inflammation.