title: Multiple extrathymic precursors contribute to T-cell development with different kinetics.
abstract: T-cell development in the thymus depends on continuous supply of T-cell progenitors from bone marrow (BM). Several extrathymic candidate progenitors have been described that range from multipotent cells to lymphoid cell committed progenitors and even largely T-lineage committed precursors. However, the nature of precursors seeding the thymus under physiologic conditions has remained largely elusive and it is not known whether there is only one physiologic T-cell precursor population or many. Here, we used a competitive in vivo assay based on depletion rather than enrichment of classes of BM-derived precursor populations, thereby only minimally altering physiologic precursor ratios to assess the contribution of various extrathymic precursors to T-lineage differentiation. We found that under these conditions multiple precursors, belonging to both multipotent progenitor (MPP) and common lymphoid progenitor (CLP) subsets have robust T-lineage potential. However, differentiation kinetics of different precursors varied considerably, which might ensure continuous thymic output despite gated importation of extrathymic precursors. In conclusion, our data suggest that the thymus functions to impose T-cell fate on any precursor capable of filling the limited number of progenitor niches.
authors.affiliation: Institute for Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Namita
authors.initials: N
authors.lastname: Saran
authors.forename: Marcin
authors.initials: M
authors.lastname: Łyszkiewicz
authors.forename: Jens
authors.initials: J
authors.lastname: Pommerencke
authors.forename: Katrin
authors.initials: K
authors.lastname: Witzlau
authors.forename: Ramin
authors.initials: R
authors.lastname: Vakilzadeh
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
authors.forename: Andreas
authors.initials: A
authors.lastname: Krueger
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D005434:Flow Cytometry; D006410:Hematopoiesis; D008213:Lymphocyte Activation; D054503:Lymphoid Progenitor Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000276:immunology; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology* / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D020395:Receptors, Interleukin-7