title: Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation.
abstract: T cell immunodeficiency is a major complication of bone marrow (BM) transplantation (BMT). Therefore, approaches to enhance T cell reconstitution after BMT are required. We have purified a hybrid cytokine, consisting of IL-7 and the β-chain of hepatocyte growth factor (HGFβ) (IL-7/HGFβ), from a unique long-term BM culture system. We have cloned and expressed the IL-7/HGFβ gene in which the IL-7 and HGFβ genes are connected by a flexible linker to generate rIL-7/HGFβ protein. Here, we show that rIL-7/HGFβ treatment enhances thymopoiesis after allogeneic BMT. Although rIL-7 treatment also enhances the number of thymocytes, rIL-7/HGFβ hybrid cytokine was more effective than was rIL-7 and the mechanisms by which rIL-7 and rIL-7/HGFβ increase the numbers of thymocytes are different. rIL-7 enhances the survival of double negative (DN), CD4 and CD8 single positive (SP) thymocytes. In contrast, rIL-7/HGFβ enhances the proliferation of the DN, SP thymocytes, as well as the survival of CD4 and CD8 double positive (DP) thymocytes. rIL-7/HGFβ treatment also increases the numbers of early thymocyte progenitors (ETPs) and thymic epithelial cells (TECs). The enhanced thymic reconstitution in the rIL-7/HGFβ-treated allogeneic BMT recipients results in increased number and functional activities of peripheral T cells. Graft-versus-host-disease (GVHD) is not induced in the rIL-7/HGFβ-treated BMT mice. Therefore, rIL-7/HGFβ may offer a new tool for the prevention and/or treatment of T cell immunodeficiency following BMT.
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut, United States of America ; University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Laijun
authors.initials: L
authors.lastname: Lai
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Yinhong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Debra
authors.initials: D
authors.lastname: Rood
mesh_terms: D064591:Allografts; D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology
chemical_list: C553307:HGF protein, mouse; D015851:Interleukin-7; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor