Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation

Laijun Lai; Mingfeng Zhang; Yinhong Song; Debra Rood

doi:10.1371/journal.pone.0082998

Recombinant IL-7/HGFβ hybrid cytokine enhances T cell recovery in mice following allogeneic bone marrow transplantation

PLoS One. 2013 Dec 12;8(12):e82998. doi: 10.1371/journal.pone.0082998. eCollection 2013.

Authors

Laijun Lai¹, Mingfeng Zhang², Yinhong Song², Debra Rood²

Affiliations

¹ 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.
² Department of Allied Health Sciences, University of Connecticut, Storrs, Connecticut, United States of America.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allografts
Animals
Bone Marrow Transplantation*
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology*
Hepatocyte Growth Factor / genetics
Hepatocyte Growth Factor / pharmacology*
Interleukin-7 / genetics
Interleukin-7 / pharmacology*
Mice
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / pharmacology*
Recovery of Function / drug effects*
Recovery of Function / immunology

Substances

HGF protein, mouse
Interleukin-7
Recombinant Fusion Proteins
Hepatocyte Growth Factor

Grants and funding

This work was supported by a grant from the Connecticut Stem Cell Research Program (10SCB12, to LL). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.