Wang Helen Y, Lee Dean A, Peng Guangyong, Guo Zhong, Li Yanchun, Kiniwa Yukiko, Shevach Ethan M, Wang Rong Fu
The Center for Cell and Gene Therapy and Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Immunity. 2004 Jan;20(1):107-18. doi: 10.1016/s1074-7613(03)00359-5.
Regulatory T cells play an important role in the maintenance of immunological self-tolerance by suppressing immune responses against autoimmune diseases and cancer. Little is known, however, about the nature of the physiological target antigens for CD4(+) regulatory T (Treg) cells. Here we report the identification of the LAGE1 protein as a ligand for tumor-specific CD4(+) Treg cell clones generated from the tumor-infiltrating lymphocytes (TILs) of cancer patients. Phenotypic and functional analyses demonstrated that they were antigen-specific CD4(+) Treg cells expressing CD25 and GITR molecules and possessing suppressive activity on the proliferative response of naive CD4(+) T cells to anti-CD3 antibody stimulation. Ligand-specific activation and cell-cell contact were required for TIL102 Treg cells to exert suppressive activity on CD4(+) effector cells. These findings suggest that the presence of tumor-specific CD4(+) Treg cells at tumor sites may have a profound effect on the inhibition of T cell responses against cancer.
调节性T细胞通过抑制针对自身免疫性疾病和癌症的免疫反应，在维持免疫自身耐受性方面发挥重要作用。然而，关于CD4(+)调节性T（Treg）细胞的生理靶抗原的性质，人们知之甚少。在此，我们报告鉴定出LAGE1蛋白是从癌症患者肿瘤浸润淋巴细胞（TIL）中产生的肿瘤特异性CD4(+)Treg细胞克隆的配体。表型和功能分析表明，它们是表达CD25和GITR分子的抗原特异性CD4(+)Treg细胞，对幼稚CD4(+)T细胞对抗CD3抗体刺激的增殖反应具有抑制活性。TIL102 Treg细胞对CD4(+)效应细胞发挥抑制活性需要配体特异性激活和细胞间接触。这些发现表明，肿瘤部位存在肿瘤特异性CD4(+)Treg细胞可能对抑制针对癌症的T细胞反应具有深远影响。
