Flt3 ligand expands lymphoid progenitors prior to recovery of thymopoiesis and accelerates T cell reconstitution after bone marrow transplantation.
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.
Wils
Evert-Jan
EJ
Department of Hematology, Erasmus Medical Center/Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3071 EA Amsterdam, the Netherlands.
Braakman
Eric
E
Verjans
Georges M G M
GM
Rombouts
Elwin J C
EJ
Broers
Annoek E C
AE
Niesters
Hubert G M
HG
Wagemaker
Gerard
G
Staal
Frank J T
FJ
Löwenberg
Bob
B
Spits
Hergen
H
Cornelissen
Jan J
JJ
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*
D000945:Antigens, Differentiation, T-Lymphocyte; C508605:IL7 protein, human; D015851:Interleukin-7; D008565:Membrane Proteins; C084881:flt3 ligand protein