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• W2090535331 abstract "In Brief Background Natural killer (NK) cells play a dichotomous role in alloimmune responses because they are known to promote both allograft survival and rejection. The aim of this study was to investigate the role of functionally distinct NK cell subsets in alloimmunity with the hypothesis that this dichotomy is explained by the functional heterogeneity of distinct NK cell subsets. Methods Because T-bet controls the maturation of NK cells from CD27high to terminally differentiated CD27low NK cells, we used Rag−/−T-bet−/− mice that lack mature CD27low NK cells to study the distinct roles of CD27low versus CD27high NK cells in a model of T cell–mediated skin transplant rejection under costimulatory blockade conditions. Results We found that T cell–reconstituted Rag1−/− recipients (possessing CD27low NK cells) show significantly prolonged allograft survival on costimulatory blockade when compared to Rag1−/−T-bet−/− mice (lacking CD27low NK cells), indicating that CD27low but not CD27high NK cells enhance allograft survival. Critically, Rag1−/−T-bet−/− recipients showed strikingly increased alloreactive memory CD8+ T cell responses, as indicated by increased CD8+ T cell proliferation and interferon-γ production. Therefore, we speculated that CD27low NK cells directly regulate alloreactive CD8+ T cell responses under costimulatory blockade conditions. To test this, we adoptively transferred CD27low NK cells into Rag1−/−T-bet−/− skin transplant recipients and found that the CD27low NK cells restore better allograft survival by inhibiting the proliferation of alloreactive interferon-γ+CD8+ T cells. Conclusions In summary, mature CD27low NK cells promote allograft survival under costimulatory blockade conditions by regulating alloreactive memory CD8+ T-cell responses. Using a fully allogeneic skin transplant model and adoptive transfer of NK cells, Lantow et al report that it is the mature CD27low NK cell subset that promotes allograft survival under co-stimulatory blockade by regulating alloreactive memory CD8+ T cell responses." @default.
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• W2090535331 date "2015-02-01" @default.
• W2090535331 modified "2023-09-27" @default.
• W2090535331 title "CD27low Natural Killer Cells Prolong Allograft Survival in Mice by Controlling Alloreactive CD8+ T Cells in a T-Bet–Dependent Manner" @default.
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• W2090535331 doi "https://doi.org/10.1097/tp.0000000000000585" @default.
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