Sun Q, Burton R L, Pollok K E, Emanuel D J, Lucas K G
The Bone Marrow Transplantation Program, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Cell Immunol. 1999 Aug 1;195(2):81-8. doi: 10.1006/cimm.1999.1514.
Umbilical cord blood (CB) is increasingly used for allogeneic hematopoietic stem cell transplantation. To determine whether viral antigen-specific cytotoxic T-lymphocytes (CTL) could be generated from the predominantly naive T-cell populations in CB, CB-derived mononuclear cells were stimulated with autologous Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines over several weeks in the presence of recombinant human interleukin-2 (IL-2). By 28 days of culture, T-lymphocytes from all six CB that had been treated with IL-2 displayed EBV-specific cytotoxicity. These cells were largely CD4(+), with complete inhibition of cytotoxicity by anti-CD3 and variable inhibition by anti-HLA DR monoclonal antibodies. The EBV-specific effectors were cloned by limiting dilution, and most of the CTL clones were CD4(+). The cytotoxicity of the CB-derived CD4(+) CTL clones was inhibited by EGTA but not by anti-Fas ligand mAb, suggesting that this cytotoxicity was mediated by perforin/granzyme B. These data indicate that virus-specific CTL can be cultivated and cloned from CB, a human T-cell source that may not have prior in vivo antigenic exposure or reactivity. This finding may have applications in adoptive immunotherapy to recipients of CB transplants.
脐带血（CB）越来越多地用于异基因造血干细胞移植。为了确定病毒抗原特异性细胞毒性T淋巴细胞（CTL）是否可以从CB中主要为初始T细胞的群体中产生，在重组人白细胞介素-2（IL-2）存在的情况下，用自体EB病毒（EBV）转化的B淋巴母细胞系刺激CB来源的单核细胞数周。培养至28天时，用IL-2处理的所有六个CB中的T淋巴细胞均显示出EBV特异性细胞毒性。这些细胞主要是CD4(+)，抗CD3可完全抑制细胞毒性，抗HLA DR单克隆抗体可产生可变抑制。通过有限稀释法克隆EBV特异性效应细胞，大多数CTL克隆为CD4(+)。CB来源的CD4(+) CTL克隆的细胞毒性被EGTA抑制，但不被抗Fas配体单克隆抗体抑制，这表明这种细胞毒性是由穿孔素/颗粒酶B介导的。这些数据表明，可以从CB中培养和克隆病毒特异性CTL，CB是一种可能没有先前体内抗原暴露或反应性的人类T细胞来源。这一发现可能在CB移植受者的过继免疫治疗中具有应用价值。
