Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: Implications for immune-mediated therapy of EBV(+) Hodgkin's disease
Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: Implications for immune-mediated therapy of EBV(+) Hodgkin's disease
复制标题
DOI：
10.1182/blood.v89.6.1978
复制
发表时间：
1997-03-15
期刊：
影响因子：
20.3
通讯作者：
Greenberg, PD
中科院分区：
文献类型：
--
作者：
Sing, AP;Ambinder, RF;Greenberg, PD
霍奇金氏病(HD)患者的恶性里德-斯特恩伯格(R-S)细胞中可检测到EB病毒基因组。R-S细胞只表达一组有限的潜伏的EB病毒蛋白，但只有LMP1和LMP2可以潜在地诱导CD8(+)细胞毒性T淋巴细胞(CTL)反应。我们已经评估了这两种蛋白是否可以作为EBV阳性(EBV(+))HD的特异性过继T细胞治疗的靶点。这一策略的成功需要R-S细胞对CD8(+)CTL的敏感性，并且能够在HD患者中检测到并潜在地扩增针对LMP1和LMP2的CTL。R-S细胞能够加工和呈递病毒蛋白，并能被特异性CTL以I类限制性方式有效地裂解。由于对LMP1和LMP2的CTL反应不代表对EBV的主要反应，我们研究了是否可以分离到针对这些蛋白质的CTL克隆，尽管在多克隆T细胞系中存在弱反应或不可检测的反应，LPM特异性克隆是通过从多克隆EBV反应T细胞系克隆或通过用表达LMP1或LMP2作为唯一EBV蛋白的细胞直接刺激外周血单核细胞(PBMC)而产生的。我们能够从HD患者中分离出针对LMP蛋白的CTL，以及R-S细胞对CTL介导的溶解的敏感性，这表明对于患有EBV(+)肿瘤的HD患者亚群来说，寻求特异性过继免疫治疗是一种可行的策略。(C)1997年由美国血液病学会主办。
A subset of Hodgkin's disease (HD) patients have detectable Epstein-Barr virus (EBV) genomes in the malignant Reed-Sternberg (R-S) cells. R-S cells express only a limited set of latent EBV proteins, but only LMP1 and LMP2 can potentially elicit a CD8(+) cytotoxic T-lymphocyte (CTL) response. We have evaluated if either of these proteins could be used as targets for specific adoptive T-cell therapy for EBV-positive (EBV(+)) HD. The success of this strategy requires that R-S cells are susceptible to lysis by CD8(+) CTL, and that CTL specific for LMP1 and LMP2 can be detected and potentially amplified in HD patients, Antigen presentation and CTL sensitivity was evaluated with an in vitro maintained, phenotypically representative R-S cell line, HDLM-2. The R-S cells were able to process and present viral proteins, and to be efficiently lysed by specific CTL in a Class I-restricted manner. Since CTL responses to LMP1 and LMP2 do not represent the dominant responses to EBV, we examined if CTL clones specific for these proteins could be isolated despite the presence of weak or nondetectable responses in polyclonal T-cell lines, LPM-specific clones were generated from individuals either by cloning from the polyclonal EBV-reactive T-cell lines or by direct stimulation of peripheral blood mononuclear cells (PBMC) with cells expressing LMP1 or LMP2 as the only EBV protein, Our ability to isolate CTL specific for LMP proteins from individuals with HD and the sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of specific adoptive immunotherapy represents a viable strategy for the subset of HD patients with EBV(+) tumors. (C) 1997 by The American Society of Hematology.