Svane I M, Nikolajsen K, Johnsen H E
Center for Cancer Immune Therapy, Department of Haematology, Copenhagen University Hospital, Herlev, Denmark.
Scand J Immunol. 2007 Oct;66(4):465-75. doi: 10.1111/j.1365-3083.2007.01993.x.
The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine induced specific immunity in multiple myeloma patients. Peripheral blood was collected from six multiple myeloma (MM) patients at serial time points in connection with treatment and during a follow-up period of 3 months. T-cell response to cytomegalovirus (CMV), varicella zoster virus (VZV) and tetanus toxoid (TT) was determined by flow cytometry analysis for CD69, TNFalpha, IFNgamma, IL-4 expression and cell proliferation. At diagnosis and prior to induction chemotherapy TNFalpha expressing T cells in 5/6 patients were found specific for CMV, 3/6 for VZV and 4/6 for TT. Serial analyses during treatment conclude impaired immune response, however, 3 months post-transplantation all but one patient had regained cytokine expressing CD8(+) T cells specific for CMV, VZV and TT. The highest percentages of cytokine responding T cells were observed after stimulation with CMV antigen. A striking observation was the low cytokine reactivity (close to zero) measured in G-CSF mobilized blood at the time of leukapheresis. In spite of a general reduction of the CD4/CD8 ratio following transplantation, recovery of antigen specific CD4(+) T cells reactivity generally occurred prior to CD8(+) recovery and often to a higher level. In conclusion, the study demonstrates that natural as well as vaccine induced specific immunity present prior to HD was regained after stem cell transplantation, hence identifying a possible window for future vaccination trials.
本研究分析了大剂量化疗（HD）和自体干细胞移植对多发性骨髓瘤患者天然免疫和疫苗诱导的特异性免疫的影响。在治疗相关的连续时间点以及3个月的随访期内，从6例多发性骨髓瘤（MM）患者采集外周血。通过流式细胞术分析CD69、TNFα、IFNγ、IL-4表达及细胞增殖情况，测定T细胞对巨细胞病毒（CMV）、水痘带状疱疹病毒（VZV）和破伤风类毒素（TT）的反应。在诊断时及诱导化疗前，发现5/6患者中表达TNFα的T细胞对CMV具有特异性，3/6对VZV具有特异性，4/6对TT具有特异性。治疗期间的系列分析表明免疫反应受损，然而，移植后3个月，除1例患者外，所有患者均恢复了对CMV、VZV和TT具有特异性的表达细胞因子的CD8(+) T细胞。在用CMV抗原刺激后，观察到细胞因子反应性T细胞的百分比最高。一个显著的观察结果是，在白细胞分离时，G-CSF动员的血液中测得的细胞因子反应性很低（接近零）。尽管移植后CD4/CD8比值普遍降低，但抗原特异性CD4(+) T细胞反应性的恢复通常先于CD8(+) T细胞，且恢复水平往往更高。总之，该研究表明，干细胞移植后恢复了HD前存在的天然免疫以及疫苗诱导的特异性免疫，因此确定了未来疫苗试验的一个可能窗口期。
