Therapies based on principles of ocular immune privilege.
Anterior chamber (AC)-associated immune deviation (ACAID) is a form of ocularderived peripheral tolerance that helps to maintain the immune privilege of the eye by suppressing both the priming and elicitation of adaptive immune responses. ACAID is known to facilitate the survival of corneal grafts and suppression autoimmune uveitis in the eye. Intravenous inoculation of in vitro generated ACAID tolerance-inducing antigen presenting cells (APCs) treated with transforming growth factor-Beta2 (tolerogenic APCs) generates the kind of T regulatory cells found in in vivo ACAID when antigen is inoculated into the AC of the eye. Here, we review the application of peripheral tolerance induction by ACAID with either AC inoculation or in vitro generated tolerogenic ACAID-APCs in suppressing ongoing Th1- and Th2-mediated immune pathogenesis in naive and presensitized hosts. Transfer of tolerogenic APCs has suppressed antigen-specific immune inflammation in animal models of experimental autoimmune encephalomyelitis, hapten immune pulmonary interstitial fibrosis, and ovalbumin-induced allergic pulmonary inflammation. The possibility of immune therapy by in vitro generated ACAID-like tolerogenic APCs in humans is discussed.
Zhang-Hoover
Jie
J
Schepens Eye Research Institute, and Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.
Stein-Streilein
Joan
J
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology; D001249:Asthma / Q000276:immunology / Q000628:therapy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D005123:Eye / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000628:therapy; D018418:Th2 Cells / Q000502:physiology; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology
D000943:Antigens, Differentiation; D053781:Transforming Growth Factor beta2; C036763:monocyte-macrophage differentiation antigen