Machnes-Maayan Diti, Lev Atar, Katz Uriel, Mishali David, Vardi Amir, Simon Amos J, Somech Raz
Pediatric Department B, Pediatric Immunology Service, Jeffrey Modell Foundation (JMF) Center, Edmond and Lily Safra Children's Hospital, Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.
Immunol Res. 2015 Mar;61(3):198-205. doi: 10.1007/s12026-014-8558-4.
The thymus is a highly specialized organ for T cell receptor (TCR) rearrangement and selection mechanisms that ensure the formation of functional and self-tolerant cells. Little is known about how peripheral blood assessment of thymic function reflects thymus activity during infancy. We compared thymic function-related markers in the thymus with those in peripheral blood in order to check their correlations. We concomitantly blood samples from immunocompetent infants who underwent cardiac surgery that involved thymectomy. The studied thymic markers included TCR excision circles (TRECs), four different TCRD (TCR delta chain) gene rearrangements, the TCR repertoire, regulatory T cells (Tregs, defined as the CD4+CD25+FOXP3+ cell population) and real-time quantitative polymerase chain reaction (RQ-PCR) mRNA expression of forkhead box P3 (FOXP3). Twenty patients were enrolled in this study. Their mean age at the time of the surgery was 3 months/5 days ± 3 months/18 days. There was a significant correlation between thymic and peripheral blood levels of TREC, all four TCRD gene rearrangements and the amount of Tregs. The levels of these parameters were significantly higher in the thymus than those detected in the peripheral blood. The TCR repertoire distribution in both samples was similar. FOXP3 mRNA levels in the thymus and peripheral blood correlated well. Our findings demonstrated a strong and significant correlation between peripheral blood and intra-thymic activity parameters during infancy. Assessment of these parameters in peripheral blood can be used to accurately estimate different intra-thymic capacities for assessing T cell function in health and disease.
胸腺是一个高度专业化的器官,负责T细胞受体(TCR)重排和选择机制,以确保功能性和自身耐受性细胞的形成。关于婴儿期外周血胸腺功能评估如何反映胸腺活动,我们知之甚少。我们比较了胸腺中与胸腺功能相关的标志物和外周血中的标志物,以检查它们之间的相关性。我们同时采集了接受涉及胸腺切除术的心脏手术的免疫功能正常婴儿的血样。研究的胸腺标志物包括TCR切除环(TRECs)、四种不同的TCRD(TCRδ链)基因重排、TCR库、调节性T细胞(Tregs,定义为CD4+CD25+FOXP3+细胞群体)以及叉头框P3(FOXP3)的实时定量聚合酶链反应(RQ-PCR)mRNA表达。本研究共纳入20例患者。他们手术时的平均年龄为3个月零5天±3个月零18天。胸腺和外周血中TREC、所有四种TCRD基因重排以及Tregs数量之间存在显著相关性。这些参数在胸腺中的水平显著高于在外周血中检测到的水平。两个样本中的TCR库分布相似。胸腺和外周血中的FOXP3 mRNA水平相关性良好。我们的研究结果表明,婴儿期外周血和胸腺内活动参数之间存在强烈且显著的相关性。对外周血中这些参数的评估可用于准确估计不同的胸腺内能力,以评估健康和疾病状态下的T细胞功能。