title: Delivery of progenitors to the thymus limits T-lineage reconstitution after bone marrow transplantation.
abstract: T-cell production depends on the recruitment of hematopoietic progenitors into the thymus. T cells are among the last of the hematopoietic lineages to recover after bone marrow transplantation (BMT), but the reasons for this delay are not well understood. Under normal physiologic conditions, thymic settling is selective and either CCR7 or CCR9 is required for progenitor access into the thymus. The mechanisms of early thymic reconstitution after BMT, however, are unknown. Here we report that thymic settling is briefly CCR7/CCR9-independent after BMT but continues to rely on the selectin ligand PSGL-1. The CCR7/CCR9 independence is transient, and by 3 weeks after BMT these receptors are again strictly required. Despite the normalization of thymic settling signals, the rare bone marrow progenitors that can efficiently repopulate the thymus are poorly reconstituted for at least 4 weeks after BMT. Consistent with reduced progenitor input to the thymus, intrathymic progenitor niches remain unsaturated for at least 10 weeks after BMT. Finally, we show that thymic recovery is limited by the number of progenitors entering the thymus after BMT. Hence, T-lineage reconstitution after BMT is limited by progenitor supply to the thymus.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Zlotoff
authors.forename: Shirley L
authors.initials: SL
authors.lastname: Zhang
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: De Obaldia
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hess
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Todd
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Logan
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR / Q000276:immunology*; D054400:Receptors, CCR7 / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
chemical_list: C119309:CC chemokine receptor 9; C515371:Ccr7 protein, mouse; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D054388:Receptors, CCR; D054400:Receptors, CCR7