Su Che-Chun, Chiu Hsiu-Hui, Chang Chia-Che, Chen Jui-Chieh, Hsu Su-Ming
Graduate Institute of Immunology, National Taiwan University College of Medicine, 1 Jen-Ai Road, Taipei, Taiwan.
Cancer Res. 2004 Mar 15;64(6):2148-52. doi: 10.1158/0008-5472.can-03-1337.
CD30 is expressed on Hodgkin's Reed-Sternberg (H-RS) cells, the tumor cells in Hodgkin's disease. Increased levels of serum CD30 are observed in Hodgkin's disease patients and are a good marker for predicting a poor prognosis and a poor response to therapy. In this study, we addressed the effect of CD30 on T cells. We showed that CD30, either as a membranous protein on H-RS cells and Chinese hamster ovary cells or as a plate-bound chimeric protein, inhibited T-cell proliferation. Anti-CD3-stimulated T cells in the presence of CD30 failed to increase tritium uptake and failed to express CD25 and CD26 and to produce interleukin 2. The inhibition of T-cell proliferation was, however, reversed with addition of exogenous interleukin 2 or pretreatment of H-RS cells with anti-CD30. Inability of T cells to express CD25 and CD26 in cocultures with H-RS cells or a plate-bound CD30 chimeric protein is in accordance with the results of immunohistochemistry on disease-involved tissues. We conclude that H-RS cells are able to inhibit the proliferation and activation of T cells through CD30-related interaction. The outcome of CD30-related interaction is an ineffective antitumor immunity, which is clearly in favor of the growth and survival of the tumor cells.
CD30在霍奇金病的肿瘤细胞——霍奇金-里德-斯腾伯格(H-RS)细胞上表达。霍奇金病患者血清CD30水平升高,是预测预后不良和治疗反应不佳的良好标志物。在本研究中,我们探讨了CD30对T细胞的影响。我们发现,CD30无论是作为H-RS细胞和中国仓鼠卵巢细胞上的膜蛋白,还是作为板结合嵌合蛋白,均能抑制T细胞增殖。在CD30存在的情况下,抗CD3刺激的T细胞未能增加氚摄取,未能表达CD25和CD26,也未能产生白细胞介素2。然而,添加外源性白细胞介素2或用抗CD30预处理H-RS细胞可逆转T细胞增殖的抑制。T细胞在与H-RS细胞或板结合的CD30嵌合蛋白共培养时无法表达CD25和CD26,这与疾病受累组织的免疫组化结果一致。我们得出结论,H-RS细胞能够通过与CD30相关的相互作用抑制T细胞的增殖和活化。与CD30相关的相互作用的结果是抗肿瘤免疫无效,这显然有利于肿瘤细胞的生长和存活。