T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events
T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events
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DOI：
10.1182/blood.v99.9.3449
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发表时间：
2002-05-01
期刊：
影响因子：
20.3
通讯作者：
Miedema, F
中科院分区：
文献类型：
--
作者：
Hazenberg, MD;Otto, SA;Miedema, F
人们普遍认为，稳态反应调节外周干细胞移植（PSCT）后T细胞的恢复。我们详细研究了一组因血液恶性肿瘤接受 PSCT 的成年患者与 T 细胞耗竭和临床事件相关的免疫恢复。最初，尽管CD4+和CD8+T细胞的数量仍然很低，但分裂中的幼稚、记忆和效应CD4(+)和CD8(+)T细胞的比例显着增加，并且很容易下降。 PSCT 后，T 细胞分裂率的增加反映了免疫激活，因为它们与传染病和移植物抗宿主病 (GVHD) 的发作有关。测量 T 细胞受体切除环 (TREC) 以监测初始 T 细胞的胸腺输出。 PSCT 后，早在幼稚 T 细胞数量显着恢复之前，平均 TREC 含量就迅速恢复正常。这与 TREC+ 初始 T 细胞的连续胸腺产生相一致，并不反映胸腺输出的稳态增加。患有 GVHD 和感染并发症的患者中 TREC 含量降低，这可能是由于增殖增加导致 TREC 稀释所致。将 TREC 和 K167 分析与再增殖动力学相结合，得出了新的见解：移植后免疫重建过程中 TREC 含量的恢复和 T 细胞分裂的增加与临床事件相关，而不是与 T 细胞耗竭的稳态适应相关。 (C) 2002 年，美国血液学会。
It is generally believed that homeostatic responses regulate T-cell recovery after peripheral stem cell transplantation (PSCT). We studied in detail immune recovery in relation to T-cell depletion and clinical events in a group of adult patients who underwent PSCT because of hematologic malignancies. Initially, significantly increased proportions of dividing naive, memory, and effector CD4(+) and CD8(+) T cells were found that readily declined, despite still very low numbers of CD4(+) and CD8+ T cells. After PSCT, increased T-cell division rates reflected immune activation because they were associated with episodes of infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision circles (TRECs) were measured to monitor thymic output of naive T cells. Mean TREC content normalized rapidly after PSCT, long before naive T-cell numbers had significantly recovered. This is compatible with the continuous thymic production of TREC+ naive T cells and does not reflect homeostatic increases of thymic output. TREC content was decreased in patients with GVHD and infectious complications, which may be explained by the dilution of TRECs resulting from increased proliferation. Combining TREC and K167 analysis with repopulation kinetics led to the novel insight that recovery of TREC content and increased T-cell division during immune reconstitution after transplantation are related to clinical events rather than to homeostatic adaptation to T-cell depletion. (C) 2002 by The American Society of Hematology.