title: A human recombinant IL-7/HGFα hybrid cytokine enhances T-cell reconstitution in mice after syngeneic bone marrow transplantation.
abstract: BACKGROUND
  T-cell regeneration after bone marrow transplantation (BMT) is often slow and incomplete. Therefore, the enhancement of T-cell reconstitution after BMT is required. We have previously described a naturally occurring hybrid cytokine consisting of interleukin (IL)-7 and the β-chain of hepatocyte growth factor (HGF) that had lymphopoietic stimulatory activity in vitro. We have also reported that a murine recombinant (r) IL-7/HGFβ protein significantly enhances T-cell regeneration in mice after BMT.
  
  
  METHODS
  To determine whether a human form of rIL-7/HGFβ has similar effects as the murine form, we have cloned and expressed the human IL-7 and HGFβ genes to produce a single-chain hrIL-7/HGFβ protein. We have also cloned and expressed a human form of hybrid cytokine containing IL-7 and the α-chain of HGF (HGFα) (hrIL-7/HGFα). We then determined their ability to enhance T-cell reconstitution in mice after BMT.
  
  
  RESULTS
  We found that hrIL-7/HGFα had higher in vitro and in vivo thymocyte-stimulatory activities than did the hrIL-7/HGFβ. Therefore, we focused on the functional properties of hrIL-7/HGFα and showed that administration of hrIL-7/HGFα significantly enhanced thymopoiesis in mice after syngeneic BMT by increasing the numbers of thymocytes, early thymocyte progenitors, and thymic epithelial cells. hrIL-7/HGFα cross-linked the IL-7 and HGF receptors on thymocytes, and the in vivo thymocyte-stimulatory activity was mediated by both receptors. Consequently, hrIL-7/HGFα treatment significantly increased the numbers of total and naïve T cells in the periphery.
  
  
  CONCLUSIONS
  In vivo administration of hrIL-7/HGFα efficiently restores thymopoiesis and naïve T-cell reconstitution in mice after syngeneic BMT.
authors.affiliation: Department of Immunology, School of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. llai@neuron.uchc.edu
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
authors.forename: Jingjun
authors.initials: J
authors.lastname: Jin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hodio
authors.forename: Irving
authors.initials: I
authors.lastname: Goldschneider
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology*; D018655:Lymphocyte Count; D038041:Lymphopoiesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D014185:Transplantation, Isogeneic
chemical_list: C066855:HGF protein, human; C508605:IL7 protein, human; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; D011993:Recombinant Fusion Proteins; C415350:interleukin-7 receptor, alpha chain; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met