MHC-Matched Corneal Allograft Rejection in an IFN-γ/IL-17–Independent Manner in C57BL/6 Mice
| Autor: | Kazuto Terai, Toshiaki Ohteki, Jun Yamada, Hideo Yagita, Yoichiro Iwakura, Junji Hamuro, Atsuki Fukushima, Shigeru Kinoshita |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Graft Rejection
C57BL/6 Pathology medicine.medical_specialty Stromal cell Neutrophils CD11c Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Corneal Transplantation Major Histocompatibility Complex Minor Histocompatibility Antigens Interferon-gamma Mice Th2 Cells Immune system Interferon medicine Animals Transplantation Homologous Hypersensitivity Delayed RNA Messenger Lymph node Cell Proliferation Mice Knockout B-Lymphocytes biology Reverse Transcriptase Polymerase Chain Reaction Macrophages Graft Survival Interleukin-17 Th1 Cells biology.organism_classification Eosinophils Mice Inbred C57BL Transplantation medicine.anatomical_structure Immunology Cytokines Interleukin 17 medicine.drug |
| Zdroj: | Investigative Opthalmology & Visual Science. 50:2139 |
| ISSN: | 1552-5783 |
| DOI: | 10.1167/iovs.08-2993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|