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

J Immunol. 2011 Feb 15;186(4):1915-22. doi: 10.4049/jimmunol.1001238. Epub 2011 Jan 5.


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.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation / immunology*
  • Bone Marrow Transplantation / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • DNA, Circular / administration & dosage
  • DNA, Circular / biosynthesis
  • DNA, Circular / genetics*
  • Hepatocyte Growth Factor / administration & dosage
  • Hepatocyte Growth Factor / biosynthesis
  • Hepatocyte Growth Factor / genetics*
  • Interleukin-7 / administration & dosage
  • Interleukin-7 / genetics*
  • Mice
  • Plasmids / administration & dosage
  • Plasmids / biosynthesis
  • Plasmids / genetics*
  • Radiation Chimera / immunology*
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Resting Phase, Cell Cycle / immunology
  • Stromal Cells / cytology
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Transplantation, Isogeneic


  • DNA, Circular
  • HGF protein, mouse
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Hepatocyte Growth Factor