γδ T cells acquire effector fates in the thymus and differentiate into cytokine-producing effectors in a Listeria model of infection independently of CD28 costimulation.
γδ T cells acquire effector fates in the thymus and differentiate into cytokine-producing effectors in a Listeria model of infection independently of CD28 costimulation.
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DOI：
10.1371/journal.pone.0063178
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hayes SM
中科院分区：
文献类型：
--
作者：
Laird RM;Wolf BJ;Princiotta MF;Hayes SM
抗原识别和CD 28共刺激都是幼稚αβ T细胞活化及其随后分化为产生精氨酸或细胞毒性效应物所必需的。值得注意的是，这种双信号模式适用于所有αβ T细胞亚群，无论它们是否在外周或胸腺中获得其效应子功能。然而，由于相互矛盾的结果，CD 28共刺激是否是γδ T细胞活化和分化所必需的仍然没有解决。考虑到γδ T细胞最近已显示在胸腺中获得其效应子命运，可以想象，矛盾的结果可以部分地通过在每个γδ T细胞效应子亚群的发育或分化中对CD 28共刺激的差异需求来解释。为了验证这一点，我们检查了CD 28在γδ T细胞效应子命运确定和功能中的作用。我们报道，尽管产生IFNγ的γδ T（γδ-IFNγ）细胞比产生IL-17的γδ T（γδ-17）细胞表达更高水平的CD 28，但CD 28缺乏对任一亚群的胸腺发育均无影响。此外，李斯特菌感染后，我们发现γδ-17和γδ-IFNγ效应子的扩增和分化在CD 28 +/+和CD 28 −/−小鼠之间相当。为了理解为什么CD 28共刺激对于γδ T细胞活化和分化是不利的，我们评估了γδ T细胞的葡萄糖摄取和利用，因为已知CD 28共刺激促进αβ T细胞中的糖酵解。重要的是，我们发现γδ T细胞比αβ T细胞表达更高的葡萄糖转运蛋白表面水平，并且当被激活时，在比激活的αβ T细胞更宽的葡萄糖浓度范围内表现出效应子功能。总之，这些数据不仅证明了γδ T细胞中葡萄糖代谢的增强，而且还解释了为什么γδ T细胞比αβ T细胞更不依赖于CD 28共刺激。
Both antigen recognition and CD28 costimulation are required for the activation of naïve αβ T cells and their subsequent differentiation into cytokine-producing or cytotoxic effectors. Notably, this two-signal paradigm holds true for all αβ T cell subsets, regardless of whether they acquire their effector function in the periphery or the thymus. Because of contradictory results, however, it remains unresolved as to whether CD28 costimulation is necessary for γδ T cell activation and differentiation. Given that γδ T cells have been recently shown to acquire their effector fates in the thymus, it is conceivable that the contradictory results may be explained, in part, by a differential requirement for CD28 costimulation in the development or differentiation of each γδ T cell effector subset. To test this, we examined the role of CD28 in γδ T cell effector fate determination and function. We report that, although IFNγ-producing γδ T (γδ-IFNγ) cells express higher levels of CD28 than IL-17-producing γδ T (γδ-17) cells, CD28-deficiency had no effect on the thymic development of either subset. Also, following Listeria infection, we found that the expansion and differentiation of γδ-17 and γδ-IFNγ effectors were comparable between CD28+/+ and CD28−/− mice. To understand why CD28 costimulation is dispensable for γδ T cell activation and differentiation, we assessed glucose uptake and utilization by γδ T cells, as CD28 costimulation is known to promote glycolysis in αβ T cells. Importantly, we found that γδ T cells express higher surface levels of glucose transporters than αβ T cells and, when activated, exhibit effector functions over a broader range of glucose concentrations than activated αβ T cells. Together, these data not only demonstrate an enhanced glucose metabolism in γδ T cells but also provide an explanation for why γδ T cells are less dependent on CD28 costimulation than αβ T cells.
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DOI：
10.1152/ajpendo.00344.2006
发表时间：
2007-05-01
影响因子：
5.1
作者：
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影响因子：
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期刊：
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影响因子：
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作者：
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2010-12-01
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