Long-Term Immune Reconstitution of Naive and Memory T Cell Pools after Haploidentical Hematopoietic Stem Cell Transplantation
Long-Term Immune Reconstitution of Naive and Memory T Cell Pools after Haploidentical Hematopoietic Stem Cell Transplantation
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DOI：
10.1016/j.bbmt.2013.01.017
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发表时间：
2013-05-01
影响因子：
4.3
通讯作者：
Sousa, Ana E.
中科院分区：
文献类型：
--
作者：
Azevedo, Rita I.;Soares, Maria V. D.;Sousa, Ana E.
对于缺乏人类白细胞抗原（HLA）匹配供体的患者，单倍相合造血干细胞移植（HSCT）是一种重要的替代方案。虽然使用单倍体相合供体越来越普遍，但在HLA不匹配的胸腺环境中产生供体来源的免疫系统的长期影响仍然很难表征。我们对一组移植后4 - 6年的单倍体相合HSCT受者的免疫重建进行了深入评估，并与相应的父母供体和年龄匹配的健康对照受试者平行。我们的数据显示，在接受者中，幼稚和记忆亚群的比例，无论是在CD 8（+）和CD 4（+）T细胞中，更接近于在年龄匹配的对照受试者中观察到的比供体。HSCT受者表现出相对较高的信号联合T细胞受体切除环水平，以及在初始CD 4（+）和初始调节性T细胞中最近胸腺迁移物富集的CD 31（+）亚群的频率较高。此外，HSCT受者的CD 8（+）、CD 4（+）和调节性T细胞显示出多样化的T细胞库。这些结果支持胸腺输出在T细胞重建中的关键作用。尽管如此，HSCT受者在初始富集的CD 4（+）T细胞群中的端粒明显短于年龄匹配的对照受试者，尽管在最分化的CD 8（+）和CD 4（+）T细胞亚群中观察到相似的端粒长度。总的来说，我们的数据表明，在单倍相合HSCT后成功实现了长期免疫重建，这一过程似乎在很大程度上依赖于从头T细胞产生。(C)2013年美国血液和骨髓移植学会。
Haploidentical hematopoietic stem cell transplantation (HSCT) constitutes an important alternative for patients lacking a human leukocyte antigen (HLA)-matched donor. Although the use of haploidentical donors is increasingly common, the long-term impact of generating a donor-derived immune system in the context of an HLA-mismatched thymic environment remains poorly characterized. We performed an in-depth assessment of immune reconstitution in a group of haploidentical HSCT recipients 4 to 6 years posttransplantation, in parallel with the respective parental donors and age-matched healthy control subjects. Our data show that the proportion of naive and memory subsets in the recipients, both within CD8(+) and CD4(+) T cells, more closely resembled that observed in age-matched control subjects than in the donors. HSCT recipients displayed relatively high signal-joint T cell receptor excision circle levels and a high frequency of the recent thymic emigrant enriched CD31(+) subset within naive CD4(+) and naive regulatory T cells. Moreover, CD8(+), CD4(+), and regulatory T cells from HSCT recipients displayed a diverse T cell repertoire. These results support a key role for thymic output in T cell reconstitution. Nevertheless, HSCT recipients had significantly shorter telomeres within a naive-enriched CD4(+) T cell population than age-matched control subjects, despite the similar telomere length observed within the most differentiated CD8(+) and CD4(+) T cell subsets. Overall, our data suggest that long-term immune reconstitution was successfully achieved after haploidentical HSCT, a process that appears to have largely relied on de novo T cell production. (C) 2013 American Society for Blood and Marrow Transplantation.