Yen Hung-Rong, Harris Timothy J, Wada Satoshi, Grosso Joseph F, Getnet Derese, Goldberg Monica V, Liang Kai-Li, Bruno Tullia C, Pyle Kristin J, Chan Siaw-Li, Anders Robert A, Trimble Cornelia L, Adler Adam J, Lin Tzou-Yien, Pardoll Drew M, Huang Ching-Tai, Drake Charles G
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
J Immunol. 2009 Dec 1;183(11):7161-8. doi: 10.4049/jimmunol.0900368. Epub 2009 Nov 16.
IL-17-secreting CD8 T cells (Tc17) have been described in several settings, but little is known regarding their functional characteristics. While Tc1 cells produced IFN-gamma and efficiently killed targets, Tc17 cells lacked lytic function in vitro. Interestingly, the small numbers of IFN-gamma-positive or IL-17/IFN-gamma-double-positive cells generated under Tc17 conditions also lacked lytic activity and expressed a similar pattern of cell surface proteins to IL-17-producing cells. As is the case for Th17 (CD4) cells, STAT3 is important for Tc17 polarization, both in vitro and in vivo. Adoptive transfer of highly purified, Ag-specific IL-17-secreting Tc17 cells into Ag-bearing hosts resulted in near complete conversion to an IFN-gamma-secreting phenotype and substantial pulmonary pathology, demonstrating functional plasticity. Tc17 also accumulated to a greater extent than did Tc1 cells, suggesting that adoptive transfer of CD8 T cells cultured in Tc17 conditions may have therapeutic potential for diseases in which IFN-gamma-producing cells are desired.
分泌白细胞介素-17的CD8 T细胞(Tc17)已在多种情况下被描述,但对其功能特性了解甚少。虽然Tc1细胞产生γ干扰素并能有效杀伤靶细胞,但Tc17细胞在体外缺乏杀伤功能。有趣的是,在Tc17条件下产生的少量γ干扰素阳性或白细胞介素-17/γ干扰素双阳性细胞也缺乏杀伤活性,并且表达与产生白细胞介素-17的细胞相似的细胞表面蛋白模式。与辅助性T细胞17(CD4)细胞情况一样,信号转导和转录激活因子3(STAT3)在体外和体内对Tc17细胞极化都很重要。将高度纯化的、抗原特异性分泌白细胞介素-17的Tc17细胞过继转移到携带抗原的宿主体内,导致其几乎完全转变为分泌γ干扰素的表型并出现严重的肺部病理改变,这表明其具有功能可塑性。与Tc1细胞相比,Tc17细胞积累的程度也更高,这表明过继转移在Tc17条件下培养的CD8 T细胞可能对需要产生γ干扰素的细胞的疾病具有治疗潜力。