Clave Emmanuel, Busson Marc, Douay Corinne, Peffault de Latour Régis, Berrou Jeannig, Rabian Claire, Carmagnat Maryvonnick, Rocha Vanderson, Charron Dominique, Socié Gérard, Toubert Antoine
Assistance Publique-Hôpitaux de Paris, Inserm Unite Mixte de Recherche, Institut Universitaire d'Hématologie, Université Paris, Diderot, France.
Blood. 2009 Jun 18;113(25):6477-84. doi: 10.1182/blood-2008-09-176594. Epub 2009 Mar 3.
Long-term T-cell reconstitution after hematopoietic stem cell transplantation (HSCT) is dependent on patient thymic function and affected by graft-versus-host disease (GVHD). To assess the impact of acute GVHD (aGVHD) on thymic function, we followed a cohort of 93 patients who received HSCT from a human histocompatibility leukocyte antigen-identical sibling, mainly for hematologic malignancies. Thymic output was measured by signal-joint T-cell receptor excision circles (sjTREC) real-time polymerase chain reaction. Absolute sjTREC number was lower at 6 months in patients with aGVHD (P = .014), associated with lower absolute counts of naive CD4 T cells at 6 and 12 months (P = .04 and .02), and persistent abnormalities in T-cell repertoire diversity. Age and aGVHD affected thymic function independently in multivariate analysis. In patients less than 25 years of age, thymic function recovered almost totally at 1 year. As a marker of thymocyte proliferation, we quantified the betaTREC generated during the T-cell receptor beta-chain recombination, in a group of 20 age-matched patients. Mean betaTREC level was reduced at 6 months in patients with aGVHD, indicating an impact on early thymic differentiation rather than on intrathymic proliferation. These data show that aGVHD or its treatment has a transient impact on thymic function in younger patients in the first months after HSCT.
造血干细胞移植（HSCT）后的长期T细胞重建依赖于患者的胸腺功能，并受移植物抗宿主病（GVHD）影响。为评估急性移植物抗宿主病（aGVHD）对胸腺功能的影响，我们对93例主要因血液系统恶性肿瘤而接受来自人类组织相容性白细胞抗原匹配同胞的HSCT患者进行了随访。胸腺输出通过信号连接T细胞受体切除环（sjTREC）实时聚合酶链反应进行测量。aGVHD患者在6个月时的绝对sjTREC数量较低（P = 0.014），这与6个月和12个月时幼稚CD4 T细胞的绝对计数较低相关（P = 0.04和0.02），并且T细胞库多样性持续异常。在多变量分析中，年龄和aGVHD独立影响胸腺功能。在年龄小于25岁的患者中，胸腺功能在1年时几乎完全恢复。作为胸腺细胞增殖的标志物，我们在一组20例年龄匹配的患者中对T细胞受体β链重组过程中产生的βTREC进行了定量。aGVHD患者在6个月时的平均βTREC水平降低，表明对早期胸腺分化而非胸腺内增殖有影响。这些数据表明，aGVHD或其治疗在HSCT后的最初几个月对年轻患者的胸腺功能有短暂影响。
