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

在动物实验中，肿瘤刺激的淋巴结细胞或脾细胞被肿瘤或抗CD3+IL-2激活，在过继免疫治疗模型中介导肿瘤消退，并以肿瘤特异性方式释放肿瘤反应型细胞因子。这些细胞毒性T细胞由几个TCRVβ亚群组成。V-β3、5、7、8、11细胞占大多数。TCRVβ8细胞在体内释放高剂量的干扰素γ和微量的IL-10，以应答肿瘤并介导肿瘤消退。相反，TCRVβ5、7、11细胞释放低水平的干扰素γ和高水平的IL-10，在体内没有抗肿瘤活性。在人类研究中，肿瘤裂解物或合成肽冲击的树突状细胞可以在体外产生肿瘤特异性CTL。在体外细胞毒实验中，这些CTL释放高水平的干扰素γ和微量的IL-10，并介导肿瘤杀伤。用合成肽冲击的树突状细胞作为肿瘤疫苗的患者的TCRVβ的使用情况表明，接种后TCRVβ的使用情况不同。在这项研究中，我证明了在小鼠和人类中，免疫T细胞基于TCRVβ的使用来表达Th1型/Th2型细胞因子模式。过继免疫治疗需要选择性激活有效的V-β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.