清髓性非血缘脐血与同胞供体造血干细胞移植后T淋巴细胞亚群及其受体重排删除环早期重建规律的比较分析

Comparative Analysis of Early Reconstitution of T-lymphocyte Subsets and T-cell Receptor Excision Cycles in Patients after Myeloablative Unrelated Cord Blood and Sibling Donor Transplantation

本研究比较分析清髓性非血缘脐血移植(UCBT)与同胞供体骨髓和/或外周血干细胞移植(BMT/PBSCT)后恶性血液病受者早期T细胞亚群及T细胞受体重排删除环(T-cell receptor excision cycles,TREC)的重建规律。用流式细胞术检测40例恶性血液病患者清髓性异基因造血干细胞移植后6个月外周血中T细胞亚群的变化,实时定量PCR检测TREC。结果表明,UCBT与BMT/PBSCT相比,在移植后1个月内CD3+、CD3+CD4+、CD3+CD8+细胞绝对值明显降低,此后无明显差别;2个月内CD3+细胞比例较低,但无明显差别。UCBT同BMT/PBSCT类似,CD3+CD4+细胞自植入开始即明显减低,2个月达最低,以后缓慢恢复,但至6个月仍未达正常;而CD3+CD8+亚群植入时已达正常水平,CD4+/CD8+比值至6个月仍低于正常。UCBT组在移植后1个月内naive T细胞明显高于BMT/PBSCT组;而在移植后3个月开始终末分化效应记忆T细胞明显高于BMT/PBSCT组,且明显高于正常对照组。移植后6个月内两组移植受者TREC均较低。结论:与同胞供体BMT/PBSCT相比较,UCBT后早期T细胞重建显著延迟,但终末效应记忆T细胞亚型水平明显升高,从而发挥着抗感染或抗白血病作用。

This study was purposed to comparatively analyze the early T-lymphocyte subsets and T-cell receptor exci- sion cycles （TREC） reconstruction in recipients with hematologic malignancies after myeloablative unrelated cord blood transplantation （UCBT） and sibling donor bone marrow and/or peripheral blood stem cell transplantation （BMT/PB- SCT）. The peripheral blood T lymphocyte subsets were detected using flow cytometry and TREC were detected using real-time quantitative PCR for 40 patients with hematologic malignancies in the first six months after myeloablative allo- genie hematopoietic stem cell transplantation. The results showed that in the first month after transplantation, the absolute counts of CD3 ＋ , CD3 ＋ CD4 ＋ , CD3 ＋ CD8 ＋ cells were lower significantly in the UCBT group than those in the BMT/ PBSCT group. And later the absolute counts of CD3 ＋ , CD3 ＋ CD4 ＋ , CD3 ＋ CD8 ＋ ceils were not different between two groups. The ratio of CD3 ＋ T subset in the peripheral blood lymphocytes of the UCBT recipients was lower, but the difference was not statistically significant within 2 months after transplantation. The ratio of CD3 ＋ CD4 ＋ cells in the pa- tients received the UCBT and BMT/PBSCT decreased obviously since engraftment happened. The CD3 ＋ CD4 ＋ cells on the 2 months after transplantation fell to the lowest level, then gradually increased, but did not reach to the normal level until 6 months after transplantation. CD3 ＋ CD8 ＋ cells were well reconstituted, rising to normal at the engraftment after transplantation, with a low CD4＋ ： CD8＋ ratio over the first 6 months after transplantation. Compared with the BMT/ PBSCT group, the naive T cells （CD3 ＋ CD4 ＋ CD45RA＋ CD62L＋ ） were more in the first month after transplantationand the terminally differentiated effector memory T cells （CD3 ＋ CD4 ＋ CD45RA ＋ CD62L- ） were more at the 3 month after transplantation in the UCBT group, and those were significantly more than the normal control group. TREC were lower and did not recovered until 6 months after transplantation in the recipients of the two groups. It is concluded that compared with sibling donor＋ BMT/PBSCT, early T cell reconstitution significantly delayes after UCBT, but the termi- nally differentiated effector memory T cells are higher after transplantation, and thus play a anti-infective or anti-leukemia role.