Azuma Takeshi, Takahashi Tsuyoshi, Kunisato Atsushi, Kitamura Tadaichi, Hirai Hisamaru
Department of Hematology and Oncology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Cancer Res. 2003 Aug 1;63(15):4516-20.
CD4+CD25+ regulatory T cells play an important role in peripheral tolerance. These cells have been reported to be capable of suppressing the response of CD4+CD25- T cells in vitro. The depletion of these cells evokes effective immune responses to tumor cells in vivo. In this study, we demonstrate that CD4+CD25+ T cells also suppress all subsets of Valpha24+NKT cells (Valpha24+CD4-CD8- double negative, Valpha24+CD4+, and Valpha24+CD8+) in both proliferation and cytokine production [IFN-gamma, interleukin-4 (IL-4), IL-13, and IL-10]. This suppression is mediated by cell-to-cell contact but not by a humoral factor or the inhibition of antigen-presenting cells. Moreover, the cytotoxic activity of Valpha24+NKT cells against some tumor cell lines is suppressed by CD4+CD25+ T cells. This finding is important in developing an effective immunotherapy for cancer.
CD4+CD25+调节性T细胞在外周免疫耐受中发挥重要作用。据报道，这些细胞在体外能够抑制CD4+CD25-T细胞的反应。去除这些细胞可在体内引发针对肿瘤细胞的有效免疫反应。在本研究中，我们证明CD4+CD25+T细胞在增殖和细胞因子产生[干扰素-γ、白细胞介素-4（IL-4）、IL-13和IL-10]方面也抑制了Vα24+自然杀伤T细胞（Vα24+CD4-CD8-双阴性、Vα24+CD4+和Vα24+CD8+）的所有亚群。这种抑制是通过细胞间接触介导的，而不是通过体液因子或对抗抗原呈递细胞来实现的。此外，CD4+CD25+T细胞抑制了Vα24+自然杀伤T细胞对某些肿瘤细胞系的细胞毒性活性。这一发现对于开发有效的癌症免疫疗法具有重要意义。
