title: In vivo administration of the recombinant IL-7/hepatocyte growth factor β hybrid cytokine efficiently restores thymopoiesis and naive T cell generation in lethally irradiated mice after syngeneic bone marrow transplantation.
abstract: Bone marrow transplantation (BMT) is often followed by a prolonged period of T cell deficiency. Therefore, the enhancement of T cell reconstitution is an important clinical goal. We have identified a novel hybrid cytokine containing IL-7 and the β-chain of hepatocyte growth factor (HGF) in the supernatant of cultured mouse BM stromal cells. We have cloned and expressed the IL-7/HGFβ gene to produce a single-chain rIL-7/HGFβ protein that stimulates the in vitro proliferation of thymocytes, early B-lineage cell, and day 12 spleen CFUs. In this study, we show that, following syngenic BMT, the in vivo administration of rIL-7/HGFβ supports the rapid and complete regeneration of the thymus and efficiently reconstitutes the pool of naive T cells having a normally diverse TCR repertoire. The rIL-7/HGFβ hybrid cytokine was significantly more effective quantitatively than was rIL-7 and differed qualitatively in its ability to cross-link c-Met and IL-7Rα and to stimulate the expansion of early thymocyte progenitors and thymic epithelial cells. It also supports the maturation and homeostatic expansion of peripheral T cells. Consequently, the in vivo administration of rIL-7/HGFβ may offer a new approach to preventing and/or correcting post-BMT T cell immune deficiency.
authors.affiliation: Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Jin
authors.forename: Irving
authors.initials: I
authors.lastname: Goldschneider
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004270:DNA, Circular / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D015851:Interleukin-7 / Q000008:administration & dosage / Q000235:genetics*; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics*; D011828:Radiation Chimera / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D014185:Transplantation, Isogeneic
chemical_list: D004270:DNA, Circular; C553307:HGF protein, mouse; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor