title: Stem cell factor consistently improves thymopoiesis after experimental transplantation of murine or human hematopoietic stem cells in immunodeficient mice.
abstract: Deficient thymopoiesis is a pivotal determinant of impaired immune competence following hematopoietic stem cell transplantation (HSCT). Stem cell factor (SCF) is essentially involved in early thymopoiesis. We evaluated whether SCF administration would improve recovery of thymopoiesis following HSCT in immunodeficient mice receiving: 1) bone marrow (BM) transplantation of congenic mice; or 2) human fetal liver HSCT in the human immune system mouse model. Following murine BM transplantation, SCF significantly enhanced thymopoiesis and peripheral T cell recovery in lymph nodes and spleen. SCF did not affect BM lymphoid progenitor recovery and/or expansion. Median thymic cellularity increased from 0.9 in PBS- to 266 × 10(4)/thymus in SCF-treated mice (p = 0.05). Following human HSCT in human immune system mice, higher thymic cellularity was observed in SCF-treated mice. Double-negative and early double-positive thymocyte subsets increased, but especially late double-positive, CD4 single-positive, and CD8 single-positive thymocyte subsets were significantly enhanced (p < 0.05). These results show that exogenous supply of SCF may significantly improve murine and human posttransplant thymopoiesis, for which the effect is probably exerted by directly promoting T cell development intrathymically rather than by enhanced entry of prethymically expanded lymphoid progenitors.
authors.affiliation: Department of Hematology, Erasmus Medical Center, Rotterdam 3075 EA, The Netherlands.
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Wils
authors.forename: Elwin J C
authors.initials: EJ
authors.lastname: Rombouts
authors.forename: Irene
authors.initials: I
authors.lastname: van Mourik
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
authors.forename: Nicolas
authors.initials: N
authors.lastname: Legrand
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000601:surgery; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019089:Stem Cell Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D019089:Stem Cell Factor