Wanke-Jellinek Lorenz, Keegan Joshua W, Dolan James W, Lederer James A
*Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; and Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
*Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA; and Department of Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
J Leukoc Biol. 2016 Mar;99(3):483-93. doi: 10.1189/jlb.4A0315-115RR. Epub 2015 Oct 1.
T cell receptor γδ cells are known to be the primary effector T cells involved in the response to bacterial infections, yet their phenotypic characteristics are not as well established as other T cell subsets. In this study, we used cytometry by time-of-flight mass cytometry to better characterize the phenotypic response of T cell receptor γδ cells to Streptococcus pneumoniae lung infection. Mice were infected, and cells from lung washouts, spleen, and lymph nodes were stained to detect cell-surface, intracellular, and signaling markers. We observed that infection caused a significant increase in T cell receptor γδ cells, which expressed high interferon-γ and interleukin-17A levels. Profiling T cell receptor γδ cells by cytometry by time-of-flight revealed that activated γδ T cells uniquely coexpressed cell-surface Gr-1, cluster of differentiation 14, and cluster of differentiation 274 (programmed death-ligand 1). Further classification of Gr-1 expression patterns on T cell receptor γδ cells demonstrated that Gr-1(+) T cell receptor γδ cells were the primary source of interferon-γ, whereas Gr-1(-) cells mostly expressed interleukin-17A. Gr-1(+) T cell receptor γδ cells also showed higher ζ-chain-associated protein kinase 70, p38, and 4eBP1 signaling in response to infection as compared with Gr-1(-) T cell receptor γδ cells. Taken together, Gr-1 expression patterns on γδ T cells in the lung provide a robust marker to differentiate interferon-γ- and interleukin-17A-producing subsets involved in the early immune response to bacterial pneumonia.
已知T细胞受体γδ细胞是参与细菌感染应答的主要效应T细胞，但其表型特征不如其他T细胞亚群那样明确。在本研究中，我们使用飞行时间质谱流式细胞术来更好地表征T细胞受体γδ细胞对肺炎链球菌肺部感染的表型应答。小鼠受到感染，对来自肺灌洗物、脾脏和淋巴结的细胞进行染色，以检测细胞表面、细胞内和信号传导标志物。我们观察到感染导致T细胞受体γδ细胞显著增加，这些细胞表达高水平的干扰素-γ和白细胞介素-17A。通过飞行时间质谱流式细胞术分析T细胞受体γδ细胞发现，活化的γδT细胞独特地共表达细胞表面的Gr-1、分化簇14和分化簇274（程序性死亡配体1）。对T细胞受体γδ细胞上Gr-1表达模式的进一步分类表明，Gr-1(+)T细胞受体γδ细胞是干扰素-γ的主要来源，而Gr-1(-)细胞大多表达白细胞介素-17A。与Gr-1(-)T细胞受体γδ细胞相比，Gr-1(+)T细胞受体γδ细胞在感染应答中还显示出更高的ζ链相关蛋白激酶70、p38和4EBP1信号传导。综上所述，肺部γδT细胞上的Gr-1表达模式为区分参与细菌性肺炎早期免疫应答的产生干扰素-γ和白细胞介素-17A的亚群提供了一个可靠的标志物。
