title: Flt3 ligand expands lymphoid progenitors prior to recovery of thymopoiesis and accelerates T cell reconstitution after bone marrow transplantation.
abstract: Deficient thymopoiesis and retarded recovery of newly developed CD4(+) T cells is one of the most important determinants of impaired immunocompetence after hemopoietic stem cell transplantation. Here we evaluated whether Fms-like tyrosine kinase 3 (Flt3) ligand (FL) alone or combined with IL-7 affects T cell recovery, thymopoiesis, and lymphoid progenitor expansion following bone marrow transplantation in immunodeficient mice. FL strongly accelerated and enhanced the recovery of peripheral T cells after transplantation of a low number of bone marrow cells. An additive effect on T cell recovery was not observed after coadministration of IL-7. Lineage(-)sca-1(+)c-kit(+)flt3(+) lymphoid progenitor cell numbers were significantly increased in bone marrow of FL-treated mice before recovery of thymopoiesis. Thymocyte differentiation was advanced to more mature stages after FL treatment. Improved T cell recovery resulted in better immunocompetence against a post-bone marrow transplantation murine CMV infection. Collectively, our data suggest that FL promotes T cell recovery by enhanced thymopoiesis and by expansion of lymphoid progenitors.
authors.affiliation: Department of Hematology, Erasmus Medical Center/Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3071 EA Amsterdam, the Netherlands.
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Wils
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.forename: Georges M G M
authors.initials: GM
authors.lastname: Verjans
authors.forename: Elwin J C
authors.initials: EJ
authors.lastname: Rombouts
authors.forename: Annoek E C
authors.initials: AE
authors.lastname: Broers
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Niesters
authors.forename: Gerard
authors.initials: G
authors.lastname: Wagemaker
authors.forename: Frank J T
authors.initials: FJ
authors.lastname: Staal
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology; D038041:Lymphopoiesis / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C508605:IL7 protein, human; D015851:Interleukin-7; D008565:Membrane Proteins; C084881:flt3 ligand protein