MHC-matched corneal allograft rejection in an IFN-gamma/IL-17-independent manner in C57BL/6 mice.
OBJECTIVE
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.
Yamada
Jun
J
Department of Ophthalmology, Meiji University of Integrative Medicine, Kyoto, Japan. jyamada@koto.kpu-m.ac.jp
Hamuro
Junji
J
Fukushima
Atsuki
A
Ohteki
Toshiaki
T
Terai
Kazuto
K
Iwakura
Yoichiro
Y
Yagita
Hideo
H
Kinoshita
Shigeru
S
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation; D016039:Corneal Transplantation; D016207:Cytokines / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D020381:Interleukin-17 / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014184:Transplantation, Homologous
D016207:Cytokines; D020381:Interleukin-17; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D007371:Interferon-gamma