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造血干细胞移植后的早期免疫重建
引用本文:朱明霞,万文丽,李海申,王晶,王艳芳,胡凯,克晓燕. 造血干细胞移植后的早期免疫重建[J]. 北京大学学报(医学版), 2016, 48(3): 505-522. DOI: 10.3969/j.issn.1671-167X.2016.03.024
作者姓名:朱明霞  万文丽  李海申  王晶  王艳芳  胡凯  克晓燕
作者单位:(北京大学第三医院血液科,北京100191)
摘    要:目的:探讨异基因造血干细胞移植(allogenic hematopoietic stem cell transplantation,allo-HSCT)和自体造血干细胞移植(autologous HSCT,auto-HSCT)患者早期免疫重建的异同。方法:收集2011年12月至2014年8月在北京大学第三医院血液科进行HSCT的恶性血液病患者31例,其中15例allo-HSCT,16例auto-HSCT;留取20名健康人外周血标本作为健康对照。采用四色流式细胞术检测两组患者移植后1年内外周血中淋巴细胞亚群的动态变化,并通过检测T细胞受体重排删除环(T cell receptor rearrangement excision circle,TREC)水平判断初始 T细胞功能。结果:移植后12个月内allo-HSCT组和auto-HSCT组患者CD4+T细胞、CD8初始T细胞、效应记忆性T细胞、CD4中枢记忆性T细胞、中期活化性T细胞以及DC重建与健康对照组比较差异有统计学意义(P<0.05),但两组患者间差异无统计学意义(P>0.05),CD8+T细胞和NK细胞迅速恢复正常水平。移植后前3个月内B细胞重建在两组患者间差异无统计学意义(P>0.05),均显著低于健康对照组(P<0.01),但从第6个月起auto HSCT组显著快于allo-HSCT组患者(P<0.05);移植后第6个月起allo-HSCT组晚期活化性T细胞表达显著高于auto-HSCT组(P<0.05),而auto-HSCT组CD4初始T细胞和CD8中枢记忆性T细胞的表达高于allo-HSCT组(P<0.05)。移植后12个月内allo-HSCT和auto-HSCT组患者外周血CD3+T细胞中TREC水平显著低于年龄相近的健康对照组(P<0.05),allo-HSCT组患者外周血CD3+T细胞中的TREC水平稍高于auto HSCT组患者,但差异无统计学意义(P>0.05)。结论:allo-HSCT和auto-HSCT患者早期免疫重建的速度和特点很相似,移植患者免疫重建主要不是由异源性移植物所决定,可能与胸腺功能受损后T细胞分化缓慢密切相关。

关 键 词:造血干细胞移植  自体移植  异基因移植  淋巴细胞亚群  免疫重建  

Early immune reconstitution after hematopoietic stem cell transplantation
ZHU Ming-xia,WAN Wen-li,LI Hai-shen,WANG Jing,WANG Yan-fang,HU Kai,KE Xiao-yan. Early immune reconstitution after hematopoietic stem cell transplantation[J]. Journal of Peking University. Health sciences, 2016, 48(3): 505-522. DOI: 10.3969/j.issn.1671-167X.2016.03.024
Authors:ZHU Ming-xia  WAN Wen-li  LI Hai-shen  WANG Jing  WANG Yan-fang  HU Kai  KE Xiao-yan
Affiliation:(Department of Hematology, Peking University Third Hospital, Beijing 100191, China )
Abstract:Objective:To search for differences in early immune reconstitution after allogenic or autologous hematopoietic stem cell transplantation (HSCT). Methods: The peripheral blood (PB) from 31 adult patients undergoing allogenic HSCT (allo-HSCT, 15 patients) or autologous HSCT (auto-HSCT, 16 patients) for the treatment of hematological malignancies and from 20 related healthy controls (HC) from December 2011 to August 2014 was used to analyze the kinetic recovery of lymphocyte subsets by means of flow cytometry during 12 months after HSCT. The T cell receptor rearrangement excision circle (TREC) levels among CD3+ T cells were measured in the patients and HC to evaluate the thymic-dependent T cell reconstitution. Results: The allo- and auto-HSCT recipients did not differ significantly in CD4+ T cells, CD8 na-ve T cells, effecter memory T cells (TEM), CD4 central memory T cells (TCM), mid-activated T cells and dendritic cells (DC)during the follow-up (P>0.05). But they both differed significantly from HC (P<0.05). CD8+ T cells and NK cells reconstructed rapidly. There was no significant difference in the numbers of B cells between the allo- and auto-HSCT groups from M1 to M3 (P>0.05). B cells in both the groups were lower than those in HC (P<0.05). The recovery of B cells in auto-HSCT group was faster than in allo-HSCT group at M6 and M12 (P<0.05). The frequencies of CD4 na-ve T cells and later activated T cells in allo-HSCT group were significantly higher than in auto-HSCT group at M6 and M12 (P<0.05). The frequencies of CD8 TCM in auto HSCT group were significantly higher than in allo HSCT group at M6 and M12 (P<0.05). The TREC levels were significantly lower than in both the groups compared with the age matched HC during the follow-up (P<0.05). No significant difference was observed between allo-HSCT and auto-HSCT groups (P>0.05). Conclusion: The differences of the nature and the speed of lymphocyte reconstitution observed between the two patents groups were minor. This leads us to conclude that in allografted patients, immune recons-titution and subpopulations of peripheral blood lymphocytes are probably not related to the allogenicity of the graft, but due to the impaired thymus functions and slow differentiation of T lymphocytes in thymus.
Keywords:Hematopoietic stem cell transplantation  Autologous transplantation  Allogenic transplanta-tion  Lymphocyte subsets  Immune reconstitution
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