Lee K Y, Goedegebuure P S, Linehan D C, Eberlein T J
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Surgery. 1995 Apr;117(4):365-72. doi: 10.1016/s0039-6060(05)80054-6.
The elucidation of CD4+ T helper (Th) cell traits is important for the understanding of immunoregulatory mechanisms in patients with cancer, in particular the Th-cell effect on cytotoxic CD8+ tumor-specific lymphocytes (CTL).
Sixty-six T-cell receptor alpha beta+/CD4+ clones were generated from tumor-infiltrating lymphocytes of five patients with melanoma and classified into subsets by cytokine production. Transwell experiments were performed to test how the soluble factors of each Th-clone subset affected the cytotoxicity of the tumor-specific CTL against autologous tumor.
Th0 clones enhanced cytotoxicity of the CD8+ CTL compared with control CTL cultured in cytokine-free medium. Th1-clone supernatant also enhanced cytotoxicity by CD8+ CTL. In contrast, Th2 clones decreased killing compared with control CTL. Replacement of the Th clones by exogenous interleukin (IL)-2 in concentrations similar to that produced by Th0 and Th1 clones enhanced cytotoxicity. However, suppression of cytotoxicity was observed when similar concentrations of IL-4 were added instead. The helper effect of Th0-soluble factors could be inhibited by anti-IL-2 antibody, whereas anti-IL-4 antibody did not show a significant enhancement.
The majority of the CD4+ tumor-infiltrating lymphocytes (Th0) in patients with melanoma enhance the CTL response to autologous tumor by their soluble factors, whereas Th2 cells suppress the CTL response.
阐明CD4+辅助性T（Th）细胞特征对于理解癌症患者的免疫调节机制至关重要，尤其是Th细胞对细胞毒性CD8+肿瘤特异性淋巴细胞（CTL）的影响。
从5例黑色素瘤患者的肿瘤浸润淋巴细胞中产生66个T细胞受体αβ+/CD4+克隆，并根据细胞因子产生情况分为不同亚群。进行Transwell实验，以测试每个Th克隆亚群的可溶性因子如何影响肿瘤特异性CTL对自体肿瘤的细胞毒性。
与在无细胞因子培养基中培养的对照CTL相比，Th0克隆增强了CD8+CTL的细胞毒性。Th1克隆的上清液也增强了CD8+CTL的细胞毒性。相反，与对照CTL相比，Th2克隆降低了杀伤作用。用浓度与Th0和Th1克隆产生的浓度相似的外源性白细胞介素（IL）-2替代Th克隆可增强细胞毒性。然而，当加入相似浓度的IL-4时，则观察到细胞毒性受到抑制。Th0可溶性因子的辅助作用可被抗IL-2抗体抑制，而抗IL-4抗体未显示出明显增强作用。
黑色素瘤患者中大多数CD4+肿瘤浸润淋巴细胞（Th0）通过其可溶性因子增强CTL对自体肿瘤的反应，而Th2细胞则抑制CTL反应。
