Lakhdar M, Thameur H, Maalej M, Ben Ayed F, Ladgham A
Unité de Recherches d'Immunologie Cellulaire, Institut National de Carcinologie-Salah Azaiez, Bab Saadoun, Tunis, Tunisia.
Cancer Immunol Immunother. 1993 Jul;37(2):131-9. doi: 10.1007/BF01517046.
A large body of evidence has suggested that the Epstein-Barr virus (EBV) is strongly associated with undifferentiated nasopharyngeal carcinoma. Immunologically, this neoplasia is characterized by the absence of anti-EBV circulating cytotoxic T lymphocytes (CTL), despite a high number of peripheral activated CD8+ cells, as previously determined in our laboratory. In order to determine whether the absence of anti-EBV CTL is related to a reduced number of circulating anti-EBV effector cells, we attempted to expand these hypothetical specific T cells by induction of proliferation with recombinant interleukin-2 (rIL-2), in the, absence of any stimulator cells. Optimal conditions for stimulation of peripheral blood lymphocytes (PBL) of nasopharyngeal patients were obtained with 100 U/ml rIL-2 during 10 days of culture. PBL treated with rIL-2 induced a selective expansion of CD8+ cells and generated a potent cytotoxicity towards autologous or HLA-compatible lymphoblastoid cell lines, used as target cells in a chromium-release thest. However, this cytolysis was non-MHC-restricted, since, the monoclonal antibodies anti-(HLA class I) and anti-(HLA class II) were inefficient in inhibiting this cytotoxicity. Interestingly, purified CD8+ cells acquired the capacity for non-MHC-restricted cytolysis.
大量证据表明,爱泼斯坦-巴尔病毒(EBV)与未分化鼻咽癌密切相关。从免疫学角度来看,尽管如我们实验室先前测定的那样,外周有大量活化的CD8+细胞,但这种肿瘤的特征是缺乏抗EBV循环细胞毒性T淋巴细胞(CTL)。为了确定抗EBV CTL的缺失是否与循环抗EBV效应细胞数量减少有关,我们尝试在没有任何刺激细胞的情况下,通过用重组白细胞介素-2(rIL-2)诱导增殖来扩增这些假设的特异性T细胞。在培养10天期间,用100 U/ml rIL-2获得了刺激鼻咽癌患者外周血淋巴细胞(PBL)的最佳条件。用rIL-2处理的PBL诱导了CD8+细胞的选择性扩增,并对自体或HLA相容的淋巴母细胞系产生了强大的细胞毒性,这些细胞系在铬释放试验中用作靶细胞。然而,这种细胞溶解不受MHC限制,因为抗(HLA I类)和抗(HLA II类)单克隆抗体在抑制这种细胞毒性方面无效。有趣的是,纯化的CD8+细胞获得了非MHC限制的细胞溶解能力。