title: Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans.
abstract: Parallels between T cell kinetics in mice and men have fueled the idea that a young mouse is a good model system for a young human, and an old mouse, for an elderly human. By combining in vivo kinetic labeling using deuterated water, thymectomy experiments, analysis of T cell receptor excision circles and CD31 expression, and mathematical modeling, we have quantified the contribution of thymus output and peripheral naive T cell division to the maintenance of T cells in mice and men. Aging affected naive T cell maintenance fundamentally differently in mice and men. Whereas the naive T cell pool in mice was almost exclusively sustained by thymus output throughout their lifetime, the maintenance of the adult human naive T cell pool occurred almost exclusively through peripheral T cell division. These findings put constraints on the extrapolation of insights into T cell dynamics from mouse to man and vice versa.
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, 3584EA, The Netherlands.
authors.forename: Ineke
authors.initials: I
authors.lastname: den Braber
authors.forename: Tendai
authors.initials: T
authors.lastname: Mugwagwa
authors.forename: Nienke
authors.initials: N
authors.lastname: Vrisekoop
authors.forename: Liset
authors.initials: L
authors.lastname: Westera
authors.forename: Ramona
authors.initials: R
authors.lastname: Mögling
authors.forename: Anne Bregje
authors.initials: AB
authors.lastname: de Boer
authors.forename: Neeltje
authors.initials: N
authors.lastname: Willems
authors.forename: Elise H R
authors.initials: EH
authors.lastname: Schrijver
authors.forename: Gerrit
authors.initials: G
authors.lastname: Spierenburg
authors.forename: Koos
authors.initials: K
authors.lastname: Gaiser
authors.forename: Erik
authors.initials: E
authors.lastname: Mul
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: An F C
authors.initials: AF
authors.lastname: Ruiter
authors.forename: Mariette T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: José A M
authors.initials: JA
authors.lastname: Borghans
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Boer
authors.forename: Kiki
authors.initials: K
authors.lastname: Tesselaar
mesh_terms: D000328:Adult; D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D002648:Child; D003903:Deuterium; D006706:Homeostasis; D006801:Humans; D007231:Infant, Newborn; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D003903:Deuterium