| Autor: |
Lin, Ming-Lee, Zhan, Yifan, Nutt, Stephen L., Brady, Jason, Wojtasiak, Magdalena, Brooks, Andrew G., Lew, Andrew M. |
| Předmět: |
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| Zdroj: |
Xenotransplantation; Nov2006, Vol. 13 Issue 6, p536-546, 11p, 5 Graphs |
| Abstrakt: |
Background: Natural killer (NK) cells have emerged as major players in anti-viral and anti-tumour immune responses. Like cytotoxic T lymphocytes (CTL), they express perforin and are potent secretors of γ-interferon (IFN- γ). However, there is conflicting evidence about their role in mediating rejection of xenogeneic tissue. Methods: A pig-to-mouse peritoneal cell model of xenotransplantation was used to investigate the effect of NK deficiency on xenograft recovery and the possible mechanisms behind this NK-mediated graft rejection. γc−/−RAG−/− mice were used as a model of NK deficiency. Additionally, NK cells were depleted in RAG−/− mice using anti-asialo GM1. The contributions of IFN- γ, perforin and NKT cells were studied using knock-out mice that were depleted in vivo of T cells. Mice were injected with 107 pig cells intraperitoneally and peritoneal fluid was assessed 5 days later for xenograft recovery and phenotypic analysis. The requirement for NK cells for xenograft rejection was also assessed using luciferase-transfected porcine cells in a renal subcapsular model of transplantation. Results: Pig cell recovery was enhanced in both γc−/−RAG−/− and NK-depleted RAG−/− mice when compared with RAG−/− control mice. IFN- γ−/− mice depleted of T cells also demonstrated superior graft survival compared with their B6 counterparts. However, there were minimal graft survival differences between Pfp−/− and B6 control mice. Similarly, a deficiency in NKT cells did not improve pig xenograft recovery from the peritoneum of these mice. Conclusions: Therefore, we conclude that NK cells, but not NKT cells, are important mediators of xenograft rejection in the peritoneal cavity, and that their role may be unmasked in the absence of T cells. The mechanism for this xenorejection appears to involve IFN- γ but is perforin independent. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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