IL-17 promotes immune privilege of corneal allografts

• Published in: The Journal of immunology (1950) 2010-10, Vol.185 (8), p.4651-4658
• Main Authors: Cunnusamy, Khrishen, Chen, Peter W, Niederkorn, Jerry Y
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Corneal Transplantation; Enzyme-Linked Immunosorbent Assay; Female; Graft Rejection - immunology; Graft Survival; Immunohistochemistry; Interleukin-17 - immunology; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Helper-Inducer - immunology; Transplantation Immunology; Transplantation, Homologous
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001576

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.