Qian Xingxing, Hu Chunxia, Han Sen, Lin Zhijie, Xiao Weiming, Ding Yanbing, Zhang Yu, Qian Li, Jia Xiaoqing, Zhu Guoqiang, Gong Weijuan
Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.
J Cell Mol Med. 2017 Jul;21(7):1431-1444. doi: 10.1111/jcmm.13072. Epub 2017 Feb 22.
CD4 NKG2D T cells are associated with tumour, infection and autoimmune diseases. Some CD4 NKG2D T cells secrete IFN-γ and TNF-α to promote inflammation, but others produce TGF-β and FasL to facilitate tumour evasion. Here, murine CD4 NKG2D T cells were further classified into NK1.1 CD4 NKG2D and NK1.1 CD4 NKG2D subpopulations. The frequency of NK1.1 CD4 NKG2D cells decreased in inflamed colons, whereas more NK1.1 CD4 NKG2D cells infiltrated into colons of mice with DSS-induced colitis. NK1.1 CD4 NKG2D cells expressed TGF-β and FasL without secreting IFN-γ, IL-21 and IL-17 and displayed no cytotoxicity. The adoptive transfer of NK1.1 CD4 NKG2D cells suppressed DSS-induced colitis largely dependent on TGF-β. NK1.1 CD4 NKG2D cells did not expressed Foxp3, CD223 (LAG-3) and GITR. The subpopulation was distinct from NK1.1 CD4 NKG2D cells in terms of surface markers and RNA transcription. NK1.1 CD4 NKG2D cells also differed from Th2 or Th17 cells because the former did not express GATA-3 and ROR-γt. Thus, NK1.1 CD4 NKG2D cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.
CD4 NKG2D T细胞与肿瘤、感染及自身免疫性疾病相关。一些CD4 NKG2D T细胞分泌干扰素-γ和肿瘤坏死因子-α以促进炎症反应，但其他细胞则产生转化生长因子-β和FasL以促进肿瘤逃逸。在此，将小鼠CD4 NKG2D T细胞进一步分为NK1.1⁺ CD4 NKG2D和NK1.1⁻ CD4 NKG2D亚群。在炎症性结肠中，NK1.1⁺ CD4 NKG2D细胞的频率降低，而更多的NK1.1⁻ CD4 NKG2D细胞浸润到右旋糖酐硫酸钠（DSS）诱导的结肠炎小鼠的结肠中。NK1.1⁻ CD4 NKG2D细胞表达转化生长因子-β和FasL，不分泌干扰素-γ、白细胞介素-21和白细胞介素-17，且无细胞毒性。NK1.1⁻ CD4 NKG2D细胞的过继转移在很大程度上依赖转化生长因子-β抑制了DSS诱导的结肠炎。NK1.1⁻ CD4 NKG2D细胞不表达叉头框蛋白3（Foxp3）、CD223（淋巴细胞活化基因-3，LAG-3）和糖皮质激素诱导肿瘤坏死因子受体（GITR）。该亚群在表面标志物和RNA转录方面与NK1.1⁺ CD4 NKG2D细胞不同。NK1.1⁻ CD4 NKG2D细胞也与辅助性T细胞2（Th2）或辅助性T细胞17（Th17）细胞不同，因为前者不表达GATA结合蛋白3（GATA-3）和维甲酸相关孤儿受体γt（ROR-γt）。因此，NK1.1⁻ CD4 NKG2D细胞表现出免疫调节功能，并且该T细胞亚群有望在临床上用于抑制炎症反应。
