Department of Microbiology and Immunology, Nippon Medical School, Tokyo 113-8602, Japan.
Cell Immunol. 2012 Dec;280(2):138-47. doi: 10.1016/j.cellimm.2012.12.008. Epub 2013 Jan 18.
Although TGF-β and IL-6 would turn CD8(+) T cells to differentiate into non-cytotoxic state, these treated cells were converted to cytolytic phenotypes after re-exposure to their antigenic epitope in vitro. Here, using spleen cells from TCR transgenic mice expressing TCRαβ genes of clone RT1 recognizing an epitope peptide (P18-I10: RGPGRAFVTI) of HIV-1 gp160, we generated CD8(+) cytotoxic T lymphocytes (CTLs) activated by re-exposure to P18-I10 after primarily cultured with TGF-β and IL-6 in vitro to examine their effector function. The CTLs, having strong cytotoxic activity in vitro, were not only resistant to Fas-FasL mediated apoptosis, but also insensitive to the suppression of their cytotoxicity by re-exposure to TGF-β in vitro. Moreover, adoptive transfer experiments indicated that the CTLs are capable of eliminating recombinant vaccinia virus expressing HIV-1 gp160 in vivo. Taken together, our data suggest that TGF-β and IL-6 may play pivotal roles in inducing apoptosis-resistant and TGF-β-insensitive CTLs in vitro.
虽然 TGF-β 和 IL-6 会使 CD8(+)T 细胞向非细胞毒性状态分化，但这些经过处理的细胞在体外重新暴露于其抗原表位时会转化为细胞毒性表型。在这里，我们使用表达 TCRαβ 基因的 TCR 转基因小鼠的脾细胞，该基因克隆 RT1 识别 HIV-1 gp160 的一个表位肽 (P18-I10: RGPGRAFVTI)，我们通过体外重新暴露于 P18-I10 来生成 CD8(+)细胞毒性 T 淋巴细胞 (CTL)，这些 CTL 经最初培养后具有很强的细胞毒性活性，具有很强的细胞毒性活性 TGF-β 和 IL-6 在体外，不仅对 Fas-FasL 介导的细胞凋亡具有抗性，而且对体外重新暴露于 TGF-β 抑制其细胞毒性不敏感。此外，过继转移实验表明，CTL 能够在体内消除表达 HIV-1 gp160 的重组痘苗病毒。总之，我们的数据表明，TGF-β 和 IL-6 可能在体外诱导凋亡抗性和 TGF-β 不敏感的 CTL 中发挥关键作用。
