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采用淋巴因子激活的杀伤细胞和低剂量白细胞介素-2进行过继免疫治疗后外周血T淋巴细胞的细胞溶解潜力

Cytolytic potential of peripheral blood T-lymphocytes following adoptive immunotherapy with lymphokine-activated killer cells and low-dose interleukin 2.

作者信息

Yoshino I, Yano T, Murata M, Ishida T, Sugimachi K, Kimura G, Nomoto K

机构信息

Department of Virology, Kyushu University, Fukuoka, Japan.

出版信息

Cancer Res. 1991 Mar 1;51(5):1494-8.

PMID:1997188
Abstract

In this study, we investigated the cytolytic activity of peripheral blood T-cells (PBT) obtained from nine patients with primary lung cancer treated by surgical adjuvant adoptive immunotherapy (AIT) with lymphokine-activated killer cells and low-dose recombinant interleukin 2 at the time of rebound lymphocytosis (24-48 h after AIT). In eight of nine patients, nonspecific cytotoxicity of peripheral blood lymphocytes significantly increased as compared with that of pre-AIT peripheral blood lymphocytes. However, purified PBT showed much less activity to kill tumor cells although they increased in number and were activated well in terms of increases in the expression of HLA-DR and interleukin 2 receptor. The cytolytic activity of post-AIT PBT was significantly enhanced when they were targeted to Fc receptor-bearing tumor cells (K562 or Daudi) with anti-CD3 (NU-T3) or anti-T-cell receptor (TCR)alpha beta (WT31) monoclonal antibody in all five patients examined. Phenotypically, the targeted cytotoxicity was predominantly mediated by CD8+ cells. The results indicated that in vivo-activated PBT by AIT could not exhibit direct cytotoxicity, but they acquired cytolytic potential, the effect of which was expressed by targeting to tumor cells.

摘要

在本研究中,我们调查了9例接受手术辅助过继性免疫疗法(AIT)(使用淋巴因子激活的杀伤细胞和低剂量重组白细胞介素2)治疗的原发性肺癌患者在淋巴细胞增多反弹时(AIT后24 - 48小时)外周血T细胞(PBT)的细胞溶解活性。9例患者中有8例,外周血淋巴细胞的非特异性细胞毒性与AIT前外周血淋巴细胞相比显著增加。然而,纯化的PBT虽然数量增加且在HLA - DR和白细胞介素2受体表达增加方面被良好激活,但对肿瘤细胞的杀伤活性却低得多。在所有检测的5例患者中,当AIT后的PBT用抗CD3(NU - T3)或抗T细胞受体(TCR)αβ(WT31)单克隆抗体靶向带有Fc受体的肿瘤细胞(K562或Daudi)时,其细胞溶解活性显著增强。从表型上看,靶向细胞毒性主要由CD8 +细胞介导。结果表明,AIT在体内激活的PBT不能表现出直接细胞毒性,但它们获得了细胞溶解潜能,其作用通过靶向肿瘤细胞来体现。

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