Paradigm shifts in the role of CD4+ T cells in keratoplasty.
Corneal transplantation is the oldest, most common, and arguably the most successful form of organ transplantation. In uncomplicated first-time cases, corneal allografts enjoy a success rate of up to 90% even though the transplants are performed without HLA matching or the use of systemic immunosuppressive drugs. In rodents, corneal allografts transplanted across entire MHC and multiple minor histocompatibility barriers enjoy long-term survival in >50% of the hosts, while skin grafts invariably undergo immune rejection. These observations are the basis for "immune privilege" of corneal transplants. In spite of this immune privilege, immune rejection can occur and remains the leading cause of corneal graft failure. Rodent models of penetrating keratoplasty have facilitated studies that have challenged, and in some cases, refuted prevailing dogmas. The long-held belief that CD4+ T helper 1 (Th1) cells were the sole mediators of corneal allograft rejection has fallen to the wayside based on studies in interferon-gamma (IFN-γ)⁻(/)⁻ mice. The dogma that biasing the alloimmune response down a Th2 pathway would enhance graft survival has also been disproven, and in fact, compelling evidence indicates that Th2-based immune rejection of corneal allografts is swifter and more intense than Th1-based rejection. Animal studies have also pre-empted emerging dogmas including the hypothesis that Th17 cells play a crucial role in allograft rejection. Instead, IL-17A appears to be necessary for corneal allograft survival. Finally, IFN-γ, and IL-17A, which were normally viewed as proinflammatory, exert the opposite effect in the context of corneal transplantation and are necessary for corneal allograft survival.
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
Khrishen
K
Cunnusamy
Peter W
PW
Chen
Jerry Y
JY
Niederkorn
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016039:Corneal Transplantation; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000276:immunology
D015703:Antigens, CD; D020381:Interleukin-17