National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan.
J Immunol. 2012 Aug 15;189(4):1671-9. doi: 10.4049/jimmunol.1103447. Epub 2012 Jul 13.
Previous studies have shown that TGF-β acts cooperatively with IL-6 to elicit a high frequency of IL-17-secreting CD4(+) T cells (termed Th17) and an elevated CD8(+)IL-17(+) T cell population (termed Tc17). These CD8(+) cells fail to behave like most cytotoxic T lymphocytes that express IFN-γ and granzyme B, but they exhibit a noncytotoxic phenotype. Although a significant increase in the number of these Tc17 cells was found in tumors, their role and interaction with other cell types remain unclear. In this study, we demonstrate that the presence of CD4(+)CD25(-) T cells, but not the CD4(+)CD25(+) (regulatory T [Treg]) cell population, significantly reduced the elicitation of Tc17 cells, possibly as a result of the induction of apoptotic signals. Importantly, these signals may be derived from soluble mediators, and the addition of anti-IL-2 restored the reduction of Tc17 cells in the presence of CD4(+)CD25(-) T cells. Finally, the elicited Tc17 and Treg cells exhibited a close association in patients with head and neck cancer, indicating that the surrounding Treg cells might maintain the survival of the Tc17 cells. Taken together, these results reveal an intriguing mechanism in which Tc17 cells are controlled by a finely tuned collaboration between the different types of CD4(+) T cells in distinct tumor microenvironments.
先前的研究表明，TGF-β与 IL-6 协同作用，引发高水平的 IL-17 分泌 CD4+T 细胞（称为 Th17）和升高的 CD8+IL-17+T 细胞群体（称为 Tc17）。这些 CD8+细胞表现出不同于大多数表达 IFN-γ和颗粒酶 B 的细胞毒性 T 淋巴细胞的非细胞毒性表型。尽管在肿瘤中发现这些 Tc17 细胞数量显著增加，但它们的作用及其与其他细胞类型的相互作用仍不清楚。在这项研究中，我们证明了 CD4+CD25-（效应）T 细胞的存在，而不是 CD4+CD25+（调节）T 细胞（Treg）群体的存在，显著降低了 Tc17 细胞的诱导，可能是由于诱导了凋亡信号。重要的是，这些信号可能来自可溶性介质，并且添加抗 IL-2 恢复了在存在 CD4+CD25-（效应）T 细胞时 Tc17 细胞的减少。最后，在头颈部癌症患者中，诱导的 Tc17 和 Treg 细胞表现出密切关联，表明周围的 Treg 细胞可能维持 Tc17 细胞的存活。总之，这些结果揭示了一种有趣的机制，即 Tc17 细胞受到不同类型 CD4+T 细胞在不同肿瘤微环境中的精细协作的控制。
