IL-17 promotes immune privilege of corneal allografts.
Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, it has been reported that corneal allograft rejection soars in IFN-γ(-/-) mice or mice treated with anti-IFN-γ mAb. Th17 is a recently described IL-17A-producing Th cell population that has been linked to renal and cardiac graft rejection, which was originally thought to be Th1-mediated. We tested the hypothesis that Th17 cells mediate corneal allograft rejection in an IL-17A-dependent fashion and unexpectedly found that depletion of IL-17A increased the incidence of rejection to 90%. We demonstrate that the exacerbated rejection following depletion of IL-17A did not result from a loss of cross-regulation of Th1 cells or exaggerated delayed-type hypersensitivity responses. Instead, inhibition of the Th1 or Th17 cell lineages promoted the emergence of a Th2 cell subset that independently mediated allograft rejection. These findings demonstrate that IL-17A is not required for corneal allograft rejection and may instead contribute to the immune privilege of corneal allografts.
Cunnusamy
Khrishen
K
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Chen
Peter W
PW
Niederkorn
Jerry Y
JY
D019264:Adoptive Transfer; D000818:Animals; D016039:Corneal Transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D020381:Interleukin-17