Alloantigens introduced into the anterior chamber of the eye induce systemic suppression of delayed hypersensitivity to third-party alloantigens through “linked recognition”

It has been recognized for over a century that the anterior chamber of the eye is endowed with unique immunological properties that permit the long-term survival of histoincompatible grafts that would otherwise be rejected at extraocular sites. Immune privilege in the anterior chamber of the eye has been attributed, at least in part, to the active down regulation of systemic delayed-type hypersensitivity (DTH) that is induced when antigens are introduced into this ocular compartment. The antigen-specific suppression of systemic DTH that is induced by anterior chamber priming has been termed anterior chamber-associated immune deviation (ACAID) and has been demonstrated with a variety of antigens. The present report summarizes a systematic evaluation of various categories of histocompatibility antigens for their capacity to induce ACAID. The results indicate that ACAID can be induced against a wide variety of alloantigens ranging from a single minor histocompatibility antigen (H-Y) to mismatches involving the entire major histocompatibility complex plus multiple minor histocompatibility loci. Further investigation revealed that it was possible to induce suppression of DTH to third-party alloantigens providing the alloantigens introduced into the anterior chamber were coexpressed with the third-party alloantigens on cells used for extraocular immunizations.