Pawelec G, Da Silva P, Max H, Kalbacher H, Schmidt H, Bruserud O, Zügel U, Baier W, Rehbein A, Pohla H
Section for Transplantation Immunology and Immunohematology, University of Tübingen, Germany.
Leuk Lymphoma. 1995 Aug;18(5-6):471-8. doi: 10.3109/10428199509059647.
Potential anti-leukemia effects mediated by T cells or by natural killer (NK) cells were investigated in chronic myelogenous leukemia (CML) patients treated with interferon-alpha. Therapy-associated modulation of T cell and NK reactivity was monitored for one year from initiation in autologous mixed lymphocyte-tumor cell reactions and cytotoxicity directed against autologous CML cells, respectively. During the course of IFN-therapy, NK activity against autologous CML cells increased steadily, whereas T cell reactivity fluctuated randomly. Despite the high level of T cell reactivity to autologous tumor cells in short-term (6 days) culture, 1) they failed to respond to synthetic peptides corresponding to the bcr/abl fusion sequence of the patient, and 2) only one proliferative T cell clone (TCC) was isolated which specifically recognized HLA-DR-matched CML cells. This TCC appeared not to recognize synthetic peptides corresponding to the bcr/abl fusion sequence of the patient; the antigen to which it responds remains unknown. To assess potential immunogenicity of bcr/abl peptides, it was attempted to sensitize T cells from normal donors in vitro. Of 109 cell lines obtained from seven different donors, eleven showed peptide-dependent proliferation. Therefore, although these results show that it is possible to isolate apparently CML-specific T cells from patients, as well as to prime T cells against tumor-specific peptide in vitro, the frequency of such T cell-mediated reactivity appears low and its relevance to anti-leukemic effects questionable. On the other hand, the strong time-dependent enhancement of natural killing of autologous CML blasts during IFN-alpha treatment, a phenomenon not observed for T cell reactivity, suggests that natural immunity may be more important in controlling disease.
在接受α干扰素治疗的慢性粒细胞白血病（CML）患者中，研究了T细胞或自然杀伤（NK）细胞介导的潜在抗白血病作用。分别在自体混合淋巴细胞-肿瘤细胞反应和针对自体CML细胞的细胞毒性实验中，从治疗开始起监测了与治疗相关的T细胞和NK反应性的调节情况，为期一年。在IFN治疗过程中，针对自体CML细胞的NK活性稳步增加，而T细胞反应性则随机波动。尽管在短期（6天）培养中T细胞对自体肿瘤细胞的反应性较高，但1）它们对与患者bcr/abl融合序列对应的合成肽无反应，并且2）仅分离出一个增殖性T细胞克隆（TCC），该克隆特异性识别HLA-DR匹配的CML细胞。该TCC似乎不识别与患者bcr/abl融合序列对应的合成肽；其反应的抗原仍然未知。为了评估bcr/abl肽的潜在免疫原性，尝试在体外使正常供体的T细胞致敏。从七个不同供体获得的109个细胞系中，有11个显示出肽依赖性增殖。因此，尽管这些结果表明有可能从患者中分离出明显的CML特异性T细胞，以及在体外使T细胞针对肿瘤特异性肽致敏，但这种T细胞介导的反应性频率似乎较低，其与抗白血病作用的相关性也值得怀疑。另一方面，在α干扰素治疗期间，自体CML原始细胞的自然杀伤作用有强烈的时间依赖性增强，这一现象在T细胞反应性中未观察到，这表明天然免疫在控制疾病方面可能更重要。
