Tang Qin, Grzywacz Bartosz, Wang Hongbo, Kataria Nandini, Cao Qing, Wagner John E, Blazar Bruce R, Miller Jeffrey S, Verneris Michael R
Department of Pediatrics, Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
J Immunol. 2008 Oct 1;181(7):4507-15. doi: 10.4049/jimmunol.181.7.4507.
The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are thought to be NK lineage restricted. Herein we show that IL-15 induces NCR expression on umbilical cord blood (UCB) T cells. NCRs were mainly on CD8(+) and CD56(+) UCB T cells. Only NKp30 was functional as demonstrated by degranulation, IFN-gamma release, redirected killing, and apoptosis. Since NCRs require adaptor proteins for function, the expressions of these adaptors were determined. The adaptors used by NKp30 and NKp46, FcepsilonR1gamma and CD3zeta, were detected in UCB T cells. There was a near absence of DAP12, the adaptor for NKp44, consistent with a hypofunctional state. NKp46 was on significantly fewer UCB T cells, possibly accounting for its lack of function. Adult peripheral blood (PB) T cells showed minimal NCR acquisition after culture with IL-15. Since UCB contains a high frequency of naive T cells, purified naive T cells from adult PB were tested. Although NKp30 was expressed on a small fraction of naive PB T cells, it was nonfunctional. In contrast to UCB, PB T cells lacked FcepsilonR1gamma expression. These results demonstrate differences between UCB and PB T cells regarding NCR expression and function. Such findings challenge the concept that NCRs are NK cell specific.
天然细胞毒性受体(NCRs)NKp30、NKp44和NKp46被认为是NK细胞系特异性的。在此我们发现,白细胞介素-15(IL-15)可诱导脐带血(UCB)T细胞表达NCRs。NCRs主要表达于CD8(+)和CD56(+)的UCB T细胞上。只有NKp30具有功能,这通过脱颗粒、γ干扰素释放、重定向杀伤和凋亡得以证实。由于NCRs发挥功能需要衔接蛋白,因此我们检测了这些衔接蛋白的表达情况。在UCB T细胞中检测到了NKp30和NKp46所使用的衔接蛋白,即FcεR1γ和CD3ζ。几乎没有检测到NKp44的衔接蛋白DAP12,这与功能低下的状态一致。NKp46在UCB T细胞上的表达显著较少,这可能是其功能缺失的原因。成人外周血(PB)T细胞在与IL-15共培养后NCR的获得量极少。由于UCB中含有高频率的初始T细胞,因此对从成人PB中纯化出的初始T细胞进行了检测。尽管NKp30在一小部分成人PB初始T细胞上有表达,但它没有功能。与UCB不同,PB T细胞缺乏FcεR1γ的表达。这些结果表明,UCB和PB T细胞在NCR表达和功能方面存在差异。这些发现挑战了NCRs是NK细胞特异性的这一概念。