CD4^+ T细胞克隆对自体非霍奇金淋巴瘤具有特异的肿瘤杀伤作用  

Cytotoxic CD4^+ T clones as effector cells in B cell non-Hodgkin's lymphoma

作　　者：糜坚青[1] 王瑾 Olivier Manches 马立恒[1] 陈钰[1] 赵维莅[1] 陈赛娟[1] 沈志祥[1] Pascal Perron Patrice Marche Jean-Jacques Sotto Thierry Bonnefoix 王振义[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院血液科上海血液学研究所 [2]Département de Cancérologie et d'hématologie,Centre Hospitalier Universitaire Michallon,Grenoble38043,France

出　　处：《内科理论与实践》2007年第1期18-25,共8页Journal of Internal Medicine Concepts & Practice

摘　　要：目的:研究CD4+ T细胞的抗肿瘤能力。方法:利用1例滤泡B淋巴细胞淋巴瘤患者的外周血淋巴细胞,将缺乏人类白细胞抗原Ⅰ(HLA-Ⅰ)的恶性CH1细胞株作为惟一的刺激源,以梯度稀释法,得到3种自体的、细胞毒性的、具有肿瘤杀伤特异性的CD4+ T细胞克隆。结果:3种T细胞克隆可以杀伤来自于新鲜恶性B细胞的自体HLA-Ⅰ分子缺乏的淋巴瘤细胞株,但却对EB病毒(EBV)阳性的正常B细胞或K562细胞无杀伤溶解作用。3种肿瘤特异杀伤的CD4+ T细胞均为TCR Vβ17-Dβ1-Jβ1.2,并具有同样的CDR3。结论:研究表明,CD4+ T细胞克隆能够被扩增,其能够特异性地杀伤从自体淋巴瘤细胞衍生的细胞株。通过产生CD4+ T细胞来杀伤肿瘤细胞及其相应的过继转移,特别是在肿瘤逃避CD8+T细胞介导的免疫杀伤作用时,CD4+ T细胞能起到替代作用。Objective To investigate the cytotoxic ability of CD4^＋ T cells in B cell non-Hodgkin＇s lymphoma（NHL）. Methods Three autologous, cytotoxic and tumor-specific CD4^＋ T cell clones derived from peripheral blood lymphocytes of a patient with follicular B-cell lymphoma were generated. These CD4^＋ T cell clones were obtained by limiting dilution from CD4^＋ PBL coeultured with the malignant HLA- Ⅰ deficient CHI cell line, which acted as the unique source of stimulator. Results The clones were capable of killing the autologous HLA- Ⅰ deficient lymphoma cells derived from fresh malignant B cells, but did not lyse the EB virus-infected autologous normal B lymphocytes or K562 cells. AB the three tumor-specific CD4^＋ clones were TCR Vβ17-Dβ1-Jβ1.2 and exhibited an identical CDR3. Conclusions CD4^＋ T cell clones which are capable of specifically lysing cells from an autologous NHL B-cell line could be generated. Activation of the CD4^＋ cytotoxic ceBs may be an immunotherapeutic strategy in case of tumor escaping to CD8^＋-mediated responses.

关 键 词：T细胞 CD4 细胞毒性 淋巴瘤 免疫治疗 

分 类 号：R733.1[医药卫生—肿瘤]