Voutsas I F, Baxevanis C N, Gritzapis A D, Missitzis I, Stathopoulos G P, Archodakis G, Banis C, Voelter W, Papamichail M
Cancer Immunology and Immunotherapy Center, Athens, Greece.
Cancer Immunol Immunother. 2000 Oct;49(8):449-58. doi: 10.1007/s002620000132.
Peripheral blood mononuclear cells (PBMC) from cancer patients were cultured in vitro with irradiated autologous tumor cells isolated from malignant effusions (mixed lymphocyte tumor cultures, MLTC) and low-dose (50 IU/ml) recombinant interleukin-2 (IL-2). The combination of IL-2 and prothymosin alpha (ProTalpha) resulted in a greater PBMC-induced response to the autologous tumor than that brought about by IL-2 alone. In particular, ProTalpha specifically enhanced the CD4+ T-cell-mediated proliferation against the autologous tumor. CD4+ T cells seemed to recognize tumor antigens presented by HLA-DR molecules expressed on the autologous monocytes, since preincubation of the latter with an anti-HLA-DR monoclonal antibody (mAb) abrogated the response. In addition, MLTC set up with IL-2 and ProTalpha also generated more MHC-class-I-restricted cytotoxic T lymphocytes (CTL) against the autologous tumor than did MLTC set up with IL-2 alone. The MLTC-induced CTL contained high levels of cytoplasmic perforin and their development was strictly dependent on the presence of both autologous CD4+ T cells and monocytes. In the absence of either population there was a strong impairment of both proliferative and cytotoxic responses which was not restored by the presence of ProTalpha. In contrast, when both cell populations were present, ProTalpha exerted optimal enhancement of CD4+ T cell proliferation, which was associated with potentiated CTL responses. Our data emphasize the role of ProTalpha for the enhancement of IL-2-induced CTL responses against autologous tumor cells. Such responses require collaborative interactions between CD4+, CD8+ T cells and monocytes as antigen-presenting cells. Our data are relevant for adoptive immunotherapeutic settings utilizing IL-2 and ProTalpha-induced autologous-tumor-specific CTL.
将癌症患者的外周血单个核细胞（PBMC）与从恶性积液中分离出的经辐照的自体肿瘤细胞（混合淋巴细胞肿瘤培养物，MLTC）以及低剂量（50 IU/ml）重组白细胞介素-2（IL-2）在体外进行培养。与单独使用IL-2相比，IL-2与胸腺素α原（ProTα）联合使用能使PBMC对自体肿瘤产生更强的反应。特别是，ProTα特异性增强了CD4⁺ T细胞介导的针对自体肿瘤的增殖。CD4⁺ T细胞似乎识别由自体单核细胞上表达的HLA-DR分子呈递的肿瘤抗原，因为将后者与抗HLA-DR单克隆抗体（mAb）预孵育可消除该反应。此外，与单独使用IL-2建立的MLTC相比，用IL-2和ProTα建立的MLTC也能产生更多针对自体肿瘤的MHC-I类限制性细胞毒性T淋巴细胞（CTL）。MLTC诱导的CTL含有高水平的细胞质穿孔素，其发育严格依赖于自体CD4⁺ T细胞和单核细胞的同时存在。在缺少任何一种细胞群体的情况下，增殖和细胞毒性反应都会受到严重损害，且ProTα的存在无法恢复这种损害。相反，当两种细胞群体都存在时，ProTα对CD4⁺ T细胞增殖发挥最佳增强作用，这与增强的CTL反应相关。我们的数据强调了ProTα在增强IL-2诱导的针对自体肿瘤细胞的CTL反应中的作用。此类反应需要CD4⁺、CD8⁺ T细胞与作为抗原呈递细胞的单核细胞之间的协同相互作用。我们的数据与利用IL-2和ProTα诱导的自体肿瘤特异性CTL的过继免疫治疗设置相关。
