Neonatal thymectomy reveals differentiation and plasticity within human naive T cells
Neonatal thymectomy reveals differentiation and plasticity within human naive T cells
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DOI：
10.1172/jci84997
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发表时间：
2016-03-01
影响因子：
15.9
通讯作者：
van Wijk, Femke
中科院分区：
文献类型：
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作者：
van den Broek, Theo;Delemarre, Eveline M.;van Wijk, Femke
幼稚T细胞的产生依赖于胸腺输出，但在成人中，幼稚T细胞池主要由外周增殖维持。幼稚T细胞长期以来被认为是相对静止的细胞;然而，最近显示IL-8产生是幼稚T细胞的标志效应子功能，至少在新生儿中是如此。这种功能特征如何与幼稚T细胞动力学和衰老有关尚不清楚。我们使用一组接受新生儿胸腺切除术的儿童和青少年，证明健康人的幼稚CD 4（+）T细胞区室在功能上是异质的，并且这种功能多样性在新生儿胸腺切除术后丢失。胸腺组织再生导致幼稚T细胞区室的功能恢复，暗示胸腺具有功能性再生能力。总之，这些数据进一步阐明了幼稚T细胞区室内的功能分化以及胸腺在人类幼稚T细胞稳态和过早衰老中的重要性。此外，这些结果影响并改变了我们目前对真正的幼稚T细胞和最近的胸腺移民的识别的理解。
The generation of naive T cells is dependent on thymic output, but in adults, the naive T cell pool is primarily maintained by peripheral proliferation. Naive T cells have long been regarded as relatively quiescent cells; however, it was recently shown that IL-8 production is a signatory effector function of naive T cells, at least in newborns. How this functional signature relates to naive T cell dynamics and aging is unknown. Using a cohort of children and adolescents who underwent neonatal thymectomy, we demonstrate that the naive CD4(+) T cell compartment in healthy humans is functionally heterogeneous and that this functional diversity is lost after neonatal thymectomy. Thymic tissue regeneration later in life resulted in functional restoration of the naive T cell compartment, implicating the thymus as having functional regenerative capacity. Together, these data shed further light on functional differentiation within the naive T cell compartment and the importance of the thymus in human naive T cell homeostasis and premature aging. In addition, these results affect and alter our current understanding on the identification of truly naive T cells and recent thymic emigrants.