Immune privilege, T-cell tolerance, and tissue-restricted autoimmunity

Abstract

The eye is one of several specialized organs/tissues that display immune privilege, i.e. sites that permit foreign tissue grafts to enjoy prolonged (or even indefinite) survival. Immune privilege is an active, rather than a passive, process in which specialized tissues/sites and the immune system collaborate in providing immune protection without the risk of immunopathogenic injury to the tissue itself. Among the mechanisms that have been found to contribute to immune privilege is tolerance of peripheral T cells. Over the past few years, investigators have demonstrated at least four different pathways by which immune privilege can lead to T-cell tolerance: clonal deletion, clonal anergy, immune deviation, and T-cell suppression. In the case of the eye, privilege exists in part because antigens introduced into the eye are captured by distinctive local antigen-presenting cells that migrate via the blood to the spleen. At that site, they generate a stereotypic systemic immune response that is deficient in CD4 + T cells that mediate delayed hypersensitivity and that help B cells to secrete complement-fixing antibodies, yet replete with CD8 + T cells that function as cytotoxic cells and as regulatory cells. This response, termed anterior chamber associated immune deviation (ACAID), is mediated by antigen-specific regulatory T cells that secrete TGFβ in an autocrine fashion and suppress effector functions of inflammogenic CD4 + T cells. Because intraocular inflammation is deleterious to vision, ACAID and immune privilege are considered to be evolutionary adaptations that enable the eye to benefit from immune protection against pathogens without suffering blindness from immune injury.