The functional heterogeneity of type 1 effector T cells in response to infection is related to the potential for IFN-γ production
The functional heterogeneity of type 1 effector T cells in response to infection is related to the potential for IFN-γ production
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DOI：
10.4049/jimmunol.174.12.7732
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Mohrs, M
中科院分区：
文献类型：
--
作者：
Mayer, KD;Mohrs, K;Mohrs, M
干扰素-γ的表达是Th1细胞和CD8(+)效应T细胞的标志，也是1型应答的标志性细胞因子。然而，目前尚不清楚T细胞产生干扰素-γ的能力是否相同，这种潜力是否在不同组织之间存在差异，以及它与其他效应器分子的产生有何关系。在本研究中，我们使用了双顺反子IFNy增强的黄色荧光蛋白(IFN-Gamma-EYFP)报告小鼠(Yeti)和MHC I类四聚体来直接在单细胞水平上定量干扰素-γ的表达。Th1细胞和CD8(+)效应T细胞的EYFP荧光甚至在细胞分裂前就具有广泛的异质性，并与干扰素-γ转录物的丰度和刺激下干扰素-γ的分泌有关。流感感染小鼠的CD4(+)和CD8(+)T细胞表现出类似的异质性干扰素-γ表达，而EYFP(高)细胞仅在感染的肺中发现。Ag特异性T细胞在所有受检组织中EYFP(+)，但其报告荧光也是异质性的，EYFP(高)细胞也局限于感染的肺。在弓形虫感染的动物中也观察到了类似的异质性，但EYFP(High)细胞仅限于不同的组织。高度EYFP荧光细胞产生高水平的促炎细胞因子和趋化因子，以及干扰素-γ，这表明它们作为一个功能单位在高度分化的效应T细胞中协同表达。
The expression of IFN-gamma is a hallmark of Th1 cells and CD8(+) effector T cells and is the signature cytokine of type 1 responses. However, it is not known whether T cells are homogeneous in their capacity to produce IFN-gamma, whether this potential varies between tissues, and how it relates to the production of other effector molecules. In the present study we used bicistronic IFNy-enhanced yellow fluorescent protein (IFN-gamma-eYFP) reporter mice (Yeti) and MHC class I tetramers to directly quantify IFN-gamma expression at the single cell level. The eYFP fluorescence of Th1 cells and CD8(+) effector T cells was broadly heterogeneous even before cell division and correlated with both the abundance of IFN-gamma transcripts and the secretion of IFN-gamma upon stimulation. CD4(+) and CD8(+) T cells of influenza-infected mice revealed a similarly heterogeneous IFN-gamma expression, and eYFP(high) cells were only found in the infected lung. Ag-specific T cells were in all examined tissues eYFP(+), but also heterogeneous in their reporter fluorescence, and eYFP(high) cells were also restricted to the infected lung. A similar heterogeneity was observed in Toxoplasma gondii-infected animals, but eYFP(high) cells were restricted to different tissues. Highly eYFP fluorescent cells produced elevated levels of proinflammatory cytokines and chemokines in addition to IFN-gamma, suggesting their coregulated expression as a functional unit in highly differentiated effector T cells.