Homeostatic control of T-cell generation in neonates

SO Schönland, JK Zimmer, CM Lopez-Benitez… - Blood, 2003 - ashpublications.org
SO Schönland, JK Zimmer, CM Lopez-Benitez, T Widmann, KD Ramin, JJ Goronzy…
Blood, 2003ashpublications.org
T cells are produced through 2 mechanisms, thymopoiesis and proliferative expansion of
postthymic T cells. Thymic output generates diversity of the pool, and proliferation achieves
optimal clonal size of each individual T cell. To determine the contribution of these 2
mechanisms to the formation of the initial T-cell repertoire, we examined neonates of 30 to
40 weeks' gestation. Peripheral T cells were in a state of high proliferative turnover. In
premature infants, 10% of T cells were dividing; the proliferation rates then declined but …
Abstract
T cells are produced through 2 mechanisms, thymopoiesis and proliferative expansion of postthymic T cells. Thymic output generates diversity of the pool, and proliferation achieves optimal clonal size of each individual T cell. To determine the contribution of these 2 mechanisms to the formation of the initial T-cell repertoire, we examined neonates of 30 to 40 weeks' gestation. Peripheral T cells were in a state of high proliferative turnover. In premature infants, 10% of T cells were dividing; the proliferation rates then declined but were still elevated in mature newborns. Throughout the third trimester, concentrations of T-cell–receptor excision circles (TRECs) were 10 per 100 T cells. Stability of TREC frequencies throughout the period of repertoire generation suggested strict regulation of clonal size to approximately 10 to 20 cells. Neonatal naive CD4+ and CD8+ T cells were explicitly responsive to IL-7; growth-promoting properties of IL-15 were selective for newborn CD8+ T cells. Neonatal T cells expressed telomerase and, in spite of the high turnover, built up a telomeric reserve. Thus, proliferative expansion, facilitated by increased cytokine responsiveness, and thymopoiesis complement each other as mechanisms of T-cell production in neonates. Maintaining optimal clonal size instead of filling the space in a lymphopenic host appears to regulate homeostatic T-cell proliferation during fetal development.
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