Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Int J Mol Med. 2010 Jan;25(1):105-11.
Ag-specific effector/memory CD8+ T cells play an important role, not only in viral eradication, but also in T cell-mediated tumor rejection. Increasing evidence suggests that TGF-beta plays a critical role in the tumor escape from immune surveillance. Although it is known that TGF-beta directly suppresses the activation of naïve T cells, the direct effects of TGF-beta on effector/memory CD8+ T cells have not yet been fully investigated. The present study evaluated the effect of TGF-beta on effector/memory CD8+ T cells using Ag-specific, mouse-derived, effector/memory CD8+ T cell clones, designated as 6C2. Notably, pretreatment of TGF-beta1 caused an approximate 100% enhancement of IFN-gamma production in response to peptide stimulation. TGFbeta-RI kinase inhibitor reduced the enhancement of peptide-induced IFN-gamma secretion by TGF-beta1. In addition, either Activin-A or BMP-4 pretreatment caused an approximate 100% enhancement of IFN-gamma production in the peptide effect. These results suggest a contradictory effect of the TGF-beta superfamily on effector/memory CD8+ T cells.
Ag 特异性效应/记忆 CD8+T 细胞在病毒清除和 T 细胞介导的肿瘤排斥中起着重要作用。越来越多的证据表明，TGF-β在肿瘤逃避免疫监视中起着关键作用。虽然已知 TGF-β直接抑制幼稚 T 细胞的激活，但 TGF-β对效应/记忆 CD8+T 细胞的直接影响尚未得到充分研究。本研究使用 Ag 特异性、源自小鼠的效应/记忆 CD8+T 细胞克隆（命名为 6C2）评估了 TGF-β对效应/记忆 CD8+T 细胞的影响。值得注意的是，TGF-β1 的预处理导致对肽刺激的 IFN-γ产生的约 100%增强。TGFbeta-RI 激酶抑制剂降低了 TGF-β1 引起的肽诱导 IFN-γ分泌的增强。此外，活化素 A 或 BMP-4 的预处理导致肽效应中 IFN-γ产生的约 100%增强。这些结果表明 TGF-β 超家族对效应/记忆 CD8+T 细胞具有相反的作用。
