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Originally published In Press as doi:10.1167/iovs.08-2993 on January 10, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:2139-2146.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2993
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MHC-Matched Corneal Allograft Rejection in an IFN-{gamma}/IL-17–Independent Manner in C57BL/6 Mice

Jun Yamada,1 Junji Hamuro,2 Atsuki Fukushima,3 Toshiaki Ohteki,4 Kazuto Terai,1 Yoichiro Iwakura,5 Hideo Yagita,6 and Shigeru Kinoshita2

1From the Department of Ophthalmology, Meiji University of Integrative Medicine, Kyoto, Japan; the 2Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; the 3Department of Ophthalmology, Kochi Medical School, Kochi, Japan; the 4Department of Immunology, Akita University School of Medicine, Akita, Japan; the 5Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and the 6Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.

PURPOSE. It has been widely accepted that Th1- and IFN-{gamma}–mediated immune responses are indispensable for corneal allograft rejection in BALB/c hosts. The present study was designed to determine the role of IFN-{gamma} and IL-17 in the rejection by C57BL/6 hosts, which display high rejection rates.

METHODS. MHC-matched or -mismatched corneal allografts were grafted onto IFN-{gamma}–knockout (GKO), IFN-{gamma}–receptor-knockout (GRKO), IL-17–knockout (IL-17KO), or wild-type (WT) C57BL/6 hosts. Graft fates were assessed clinically and histologically. At appropriate time intervals after allografting, RNA was isolated from corneal graft parenchymal and stromal tissues and cervical lymph nodes. The cytokine mRNA levels of Th1, -2, and -17 type were analyzed by real-time PCR.

RESULTS. No significantly prolonged allograft survival was observed in any combinations. The rejected MHC-mismatched corneas in GKO elicited intensive infiltration of eosinophils, CD11b+ macrophages, and B cells, but few Gr-1+CD11c– neutrophils. In contrast, rejected MHC-matched corneas in GKO hosts, as well as GRKO and WT hosts, elicited intensive infiltration of CD11b+ macrophages and Gr-1+CD11c– neutrophils, but no B220+ B cells and eosinophils. At 1 week after MHC-matched allografting, mRNA levels of IL-6 and IL-17A in the lymph node were extensively upregulated in GKO hosts. It is of interest that anti–IFN-{gamma} treatment did not improve the allograft survival in IL-17KO hosts.

CONCLUSIONS. IFN-{gamma} and IL-17 play no critical role in the development of minor-specific allograft rejection in C57BL/6 mice. This indicates the presence of sophisticated rejection mechanisms that are still elusive and cannot be ascribed simply to Th1, -2, or -17.






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