title: Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice.
abstract: Development of T cells in the thymus requires continuous importation of T-lineage progenitors from the bone marrow via the circulation. Following bone marrow transplant, recovery of a normal peripheral T-cell pool depends on production of naïve T cells in the thymus; however, delivery of progenitors to the thymus limits T-lineage reconstitution. Here, we examine homing of intravenously delivered progenitors to the thymus following irradiation and bone marrow reconstitution. Surprisingly, following host conditioning by irradiation, we find that homing of lymphoid-primed multipotent progenitors and common lymphoid progenitors to the thymus decreases more than 10-fold relative to unirradiated mice. The reduction in thymic homing in irradiated mice is accompanied by a significant reduction in CCL25, an important chemokine ligand for thymic homing. We show that pretreatment of bone marrow progenitors with CCL25 and CCL21 corrects the defect in thymic homing after irradiation and promotes thymic reconstitution. These data suggest new therapeutic approaches to promote T-cell regeneration.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Shirley L
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Sugata
authors.initials: S
authors.lastname: Manna
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Zlotoff
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Jerrod L
authors.initials: JL
authors.lastname: Bryson
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000008:administration & dosage*; D019742:Chemokines, CC / Q000008:administration & dosage*; D005260:Female; D054503:Lymphoid Progenitor Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D019172:Transplantation Conditioning
chemical_list: C491541:Ccl25 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC