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 Kinoshita 2
1 Ophthalmology, Meiji University of Integrative Medicine, Kyoto, Japan
2 Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
3 Ophthalmology, Kochi Medical School, Kochi, Japan
4 Immunology, Akita University School of Medicine, Akita, Japan
5 Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
6 Immunology, Juntendo University School of Medicine, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: jyamada{at}koto.kpu-m.ac.jp.
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Abstract |
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Purpose: It has been widely accepted that Th1- and IFN-gamma-mediated immune responses are indispensable for the corneal allograft rejection of 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 that display high rejection rates.
METHODS: MHC-matched or MHC-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, Th2, and Th17 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 one week after MHC-matched allografting, mRNA levels of IL-6 and IL-17A in the lymph node were extensively up-regulated in GKO hosts. It is of interest that anti-IFN-gamma-treatment did not improve the allograft survival in IL-17KO hosts.
CONCLUSIONS: Both 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 not ascribed simply to Th1, Th2, or Th17.
Key Words:
corneal transplantation, immunopathology, cytokine
