Li Hui, Yu Jin-Pu, Cao Shui, Wei Feng, Zhang Peng, An Xiu-Mei, Huang Zong-Tang, Ren Xiu-Bao
Department of Immunology, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 30060, China,
J Clin Immunol. 2007 May;27(3):317-26. doi: 10.1007/s10875-007-9076-0. Epub 2007 Apr 28.
: CD(4) (+)CD(25) (+) regulatory T cells (Tregs) have been shown to inhibit cytotoxic lymphocytes-mediated immune responses. Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches. Therefore, the purpose of this report was to determine the effect of Tregs on CIK cell growth and CIK-induced cytotoxicity for inhibition of tumor growth in vivo as well as in vitro. After depletion of CD(4) (+)CD(25) (+) cells before culture, the proliferation and cytotoxicity of CIK cells, which indicated in bromodeoxyuridine (BrdU) and lactic dehydrogenase (LDH) assays, were significantly increased. Depletion of CD(4) (+)CD(25) (+) cells preculture also enhanced the suppression effect on the lung cancer cells inoculated in experimental animals. Blockage of glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor beta1 (TGF-beta1) by antibodies partially abrogated the suppressive effect of CD(4) (+)CD(25) (+) cells on CIK. These results indicated that Tregs could inhibit the antitumor activity of CIK cells. The molecules TGF-beta and GITR may contribute to the suppressive function of CD(4) (+)CD(25) (+) cells.
CD4(+)CD25(+)调节性T细胞（Tregs）已被证明可抑制细胞毒性淋巴细胞介导的免疫反应。细胞因子诱导的杀伤（CIK）细胞对过继性免疫治疗方法有很大影响。因此，本报告的目的是确定Tregs对CIK细胞生长和CIK诱导的细胞毒性的影响，以抑制体内和体外肿瘤生长。在培养前去除CD4(+)CD25(+)细胞后，CIK细胞的增殖和细胞毒性（通过溴脱氧尿苷（BrdU）和乳酸脱氢酶（LDH）测定表明）显著增加。预培养时去除CD4(+)CD25(+)细胞也增强了对接种于实验动物的肺癌细胞的抑制作用。用抗体阻断糖皮质激素诱导的肿瘤坏死因子受体（GITR）和转化生长因子β1（TGF-β1）可部分消除CD4(+)CD25(+)细胞对CIK的抑制作用。这些结果表明，Tregs可抑制CIK细胞的抗肿瘤活性。TGF-β和GITR分子可能有助于CD4(+)CD25(+)细胞的抑制功能。
