CHARACTERIZATION OF TCR Vβ REPERTOIRE AND TH1/TH2 CYTOKINE RELEASE OF TUMOR-SPECIFIC CYTOTOXIC T CELLS

在动物实验中，在过继免疫治疗模型中，肿瘤引发的淋巴结细胞或脾细胞被肿瘤或抗cd3 + IL-2介导的肿瘤消退激活，并以肿瘤特异性方式释放肿瘤反应性1型细胞因子。这些细胞毒性T细胞（CTL）由几个TCR Vβ亚群组成。整个群体大部分由Vβ3、5、7、8和11+细胞组成。在体内，TCR Vβ8+细胞释放大量IFNγ和少量IL-10，响应肿瘤和介导的肿瘤消退。相比之下，TCR v β 5,7,11 +细胞释放少量IFNγ，高水平IL-10，无体内抗肿瘤反应性。在人体研究中，肿瘤特异性ctl可以在体外用肿瘤裂解液或合成肽脉冲树突状细胞生成。在体外细胞毒实验中，这些ctl释放大量IFNγ和少量IL-10，介导肿瘤溶解。合成肽脉冲树突状细胞作为肿瘤疫苗的患者的TCR Vβ使用情况表明接种后TCR Vβ的使用情况不同。在这项研究中，我证明了基于小鼠和人的TCR Vβ使用，免疫T细胞表达Th1/Th2细胞因子模式。过继免疫治疗需要选择性激活有效的Vβ亚群。

In animal study, tumor-primed lymph node cells or splenocyte activated with tumor or anti-CD3 plus IL-2 mediated tumor regression in adoptive immunotherapy models and release tumor-reactive Type 1 cytokines in tumor specific manner. These cytotoxic T cells (CTL) consist of the several TCR Vβ subpopulations. The majority of the whole population were composed of Vβ3, 5, 7, 8 and 11+cells. TCR Vβ8+cells released high amounts of IFNγ with minimal amounts of IL-10 in response to tumor and mediated tumor regression in vivo. In contrast, TCR Vβ5, 7, 11+cells released low amounts of IFNγ with high level of IL-10 and had no in vivo antitumor reactivity. In human study, tumor-specific CTLs could be generated with tumor lysate or synthetic peptide-pulsed dendritic cells in vitro. These CTLs released high amount of IFNγ with minimal amounts of IL-10 and mediated tumor lysis in vitro cytotoxic assay. TCR Vβ usage of the patients with synthetic peptide-pulsed dendritic cell as cancer vaccine indicated the different profiles of TCR Vβ usage after vaccination. In this study, I demonstrated that Th1/Th2 cytokine patterns are expressed by immune T cells based upon TCR Vβ usage in mouse and human. Selective activation of effective Vβ subpopulation would be required for adoptive immunotherapy.