Tahir S M, Cheng O, Shaulov A, Koezuka Y, Bubley G J, Wilson S B, Balk S P, Exley M A
Cancer Biology Program, Hematology/Oncology Division, Department of Medicine, Beth Israel-Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
J Immunol. 2001 Oct 1;167(7):4046-50. doi: 10.4049/jimmunol.167.7.4046.
Invariant NK T cells express certain NK cell receptors and an invariant TCRalpha chain specific for the MHC class I-like CD1d protein. These invariant NK T cells can regulate diverse immune responses in mice, including antitumor responses, through mechanisms including rapid production of IL-4 and IFN-gamma, but their physiological functions remain uncertain. Invariant NK T cells were markedly decreased in peripheral blood from advanced prostate cancer patients, and their ex vivo expansion with a CD1d-presented lipid Ag (alpha-galactosylceramide) was diminished compared with healthy donors. Invariant NK T cells from healthy donors produced high levels of both IFN-gamma and IL-4. In contrast, whereas invariant NK T cells from prostate cancer patients also produced IL-4, they had diminished IFN-gamma production and a striking decrease in their IFN-gamma:IL-4 ratio. The IFN-gamma deficit was specific to the invariant NK T cells, as bulk T cells from prostate cancer patients produced normal levels of IFN-gamma and IL-4. These findings support an immunoregulatory function for invariant NK T cells in humans mediated by differential production of Th1 vs Th2 cytokines. They further indicate that antitumor responses may be suppressed by the marked Th2 bias of invariant NK T cells in advanced cancer patients.
不变自然杀伤T细胞表达某些自然杀伤细胞受体以及一种对MHC I类样CD1d蛋白具有特异性的不变TCRα链。这些不变自然杀伤T细胞可通过包括快速产生IL-4和IFN-γ等机制，在小鼠中调节多种免疫反应，包括抗肿瘤反应，但其生理功能仍不确定。晚期前列腺癌患者外周血中的不变自然杀伤T细胞明显减少，与健康供体相比，其用CD1d呈递的脂质抗原（α-半乳糖神经酰胺）进行体外扩增的能力降低。健康供体的不变自然杀伤T细胞可产生高水平的IFN-γ和IL-4。相比之下，虽然前列腺癌患者的不变自然杀伤T细胞也产生IL-4，但其IFN-γ产生减少，且IFN-γ与IL-4的比值显著降低。IFN-γ缺乏是不变自然杀伤T细胞所特有的，因为前列腺癌患者的大量T细胞可产生正常水平的IFN-γ和IL-4。这些发现支持了人类中不变自然杀伤T细胞通过Th1与Th2细胞因子的差异产生所介导的免疫调节功能。它们进一步表明，晚期癌症患者中不变自然杀伤T细胞明显的Th2偏向可能会抑制抗肿瘤反应。
