SYMPOSIUM 2New Insights into Prevention of Donor-specific Corneal Graft RejectionYamada, Jun M.D., Ph.D.; Streilein, J. Wayne M.D.Author Information From Schepens Eye Research Institute (J.Y., J.W.S.), Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, U.S.A.; and the Department of Ophthalmology (J.Y.), Kyoto Prefectural University of Medicine, Kyoto, Japan. Submitted June 26, 2000. Revision received August 29, 2000. Accepted August 30, 2000. Address correspondence and reprint requests to Dr. J. Yamada, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji-agaru Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan. E-mail: firstname.lastname@example.org Cornea: November 2000 - Volume 19 - Issue 6 - p S177-S182 Buy Abstract Allogeneic corneal grafts placed in “high-risk” human eyes have a very poor prognosis, and even intensive systemic immunosuppressive therapy is often of no avail. Because corneal transplants are the most common type of clinical grafting performed in humans and because failure of corneal grafts in “high-risk” eyes is a prominent cause of blindness, understanding the immunologic bases of graft rejection and of developing donor-specific suppression are worthy goals for research. The development of rodent models to experimentally explore orthotopic cornea transplants engendered significant new knowledge during the 1990s. Due to the factors responsible for ocular immune privilege, it has been found that minor histocompatibility antigens, rather than antigens encoded within the major histocompatibility complex, are the most important initiators of alloimmunity after orthotopic corneal transplants. Minor histocompatibility antigens are presented to the recipient immune system by antigen-presenting cells that migrate into the graft from the limbus. Peptides derived from processing of minor histocompatibility antigens are loaded onto “self” MHC molecules and presented to recipient T cells by the so-called indirect pathway of allorecognition. It is now established that T lymphocytes (and cell-mediated immunity) rather than antibodies (and humoral immunity) are chiefly responsible for the destructive alloimmunity that follows orthotopic corneal grafting in rodents. Moreover, CD4+T cells of the T helper type 1 phenotype (rather than CD8+cytotoxic T cells) that effect delayed-type hypersensitivity are the more important proximate mediators of corneal graft rejection. Armed with this information, our laboratory has developed novel strategies to prevent rejection of orthotopic corneal transplants. Our hope is that we will discover donor-specific immunosuppressive therapy that will be useful in human beings. Copyright © 2000 Wolters Kluwer Health, Inc. All rights reserved.