IMMUNOLOGICAL NONRESPONSIVENESS AND ACQUISITION OF TOLERANCE IN RELATION TO IMMUNE PRIVILEGE IN THE EYE

Immune privilege is a dynamic, physiological process that enables the eye to accept foreign tissue grafts in an unprecedented fashion. Privilege is actively acquired and maintained by immune regulatory forces that represent an important form of antigen-specific immunological tolerance. Privilege in the eye results from eye-dependent modifications in the induction (afferent limb) and expression (efferent limb) of immunity to intraocular antigens. The eye-dependent features that are important in privilege include integrity of the blood-ocular barrier, the virtual absence of lymphatics, an afferent drainage pathway that is almost exclusively via the blood vasculature, and an immunosuppressive intraocular microenvironment. This microenvironment is comprised of a variety of cytokines and neuropeptides that (1) impair antigen-driven activation of primed and alloreactive T cells, (2) suppress effector functions of activated macrophages, and (3) modify the antigen processing and presenting properties of indigenous, bone-marrow-derived professional antigen presenting cells. Eye-derived antigenic signals, which escape when local antigen presenting cells migrate via the blood to the spleen, selectively activate regulatory T cells that impair the development of antigen-specific delayed hypersensitivity and complement fixing antibodies, a phenomenon termed anterior chamber associated immune deviation (ACAID). ACAID has been implicated in the extraordinary success of orthotopic corneal allografts, as well as the prolonged intraocular survival enjoyed by transplants of retinal tissues. The active features of immune privilege can be exploited to secure successful corneal and retinal transplantation.