Immunoregulatory effects of CD4+ T helper subsets in human melanoma.
Immunoregulatory effects of CD4+ T helper subsets in human melanoma.
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DOI：
10.1016/s0039-6060(05)80054-6
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发表时间：
1995-04
期刊：
影响因子：
3.8
通讯作者：
K. Lee;P. Goedegebuure;D. Linehan;T. Eberlein
中科院分区：
文献类型：
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作者：
K. Lee;P. Goedegebuure;D. Linehan;T. Eberlein
背景阐明CD 4 +T辅助细胞（Th）特性对于理解肿瘤患者的免疫调节机制，特别是Th细胞对细胞毒性CD 8+肿瘤特异性淋巴细胞（CTL）的作用具有重要意义。结果与对照组相比，Th 0克隆增强了CD 8 +CTL对自体肿瘤细胞的杀伤活性。Th 1克隆上清也能增强CD 8 +CTL的细胞毒活性。相反，与对照CTL相比，Th 2克隆降低了杀伤。用与Th 0和Th 1克隆产生的浓度相似的外源性白细胞介素（IL）-2替代Th克隆增强细胞毒性。然而，当加入类似浓度的IL-4时，观察到细胞毒性的抑制。Th 0可溶性因子的辅助效应可被抗IL-2抗体抑制，而抗IL-4抗体没有表现出显着enhancement.ConclusionsThe大多数的CD 4+肿瘤浸润性淋巴细胞（Th 0）在黑色素瘤患者增强CTL反应自体肿瘤的可溶性因子，而Th 2细胞抑制CTL反应。
BackgroundThe 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).MethodsSixty-six T-cell receptor αβ+/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.ResultsTh0 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.ConclusionsThe 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.