Homeostatic control of T-cell generation in neonates.
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.
Schönland
Stefan O
SO
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Zimmer
Julia K
JK
Lopez-Benitez
Consuelo M
CM
Widmann
Thomas
T
Ramin
Kirk D
KD
Goronzy
Jörg J
JJ
Weyand
Cornelia M
CM
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006411:Hematopoiesis, Extramedullary; D006706:Homeostasis; D006801:Humans; D007231:Infant, Newborn / Q000097:blood / Q000276:immunology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D019409:Interleukin-15 / Q000096:biosynthesis / Q000494:pharmacology; D015851:Interleukin-7 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis
D019409:Interleukin-15; D015851:Interleukin-7; D007334:Insulin-Like Growth Factor I; D019098:Telomerase