Recombinant IL-7/HGF? 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 ?-chain of hepatocyte growth factor (HGF?) (IL-7/HGF?), from a unique long-term BM culture system. We have cloned and expressed the IL-7/HGF? gene in which the IL-7 and HGF? genes are connected by a flexible linker to generate rIL-7/HGF? protein. Here, we show that rIL-7/HGF? treatment enhances thymopoiesis after allogeneic BMT. Although rIL-7 treatment also enhances the number of thymocytes, rIL-7/HGF? hybrid cytokine was more effective than was rIL-7 and the mechanisms by which rIL-7 and rIL-7/HGF? 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/HGF? enhances the proliferation of the DN, SP thymocytes, as well as the survival of CD4 and CD8 double positive (DP) thymocytes. rIL-7/HGF? treatment also increases the numbers of early thymocyte progenitors (ETPs) and thymic epithelial cells (TECs). The enhanced thymic reconstitution in the rIL-7/HGF?-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/HGF?-treated BMT mice. Therefore, rIL-7/HGF? may offer a new tool for the prevention and/or treatment of T cell immunodeficiency following BMT.

SUBMITTER: Lai L 

PROVIDER: S-EPMC3861470 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature