In vivo administration of recombinant BTNL2-Fc fusion protein ameliorates graft-versus-host disease in mice

Cell Immunol. 2019 Jan:335:22-29. doi: 10.1016/j.cellimm.2018.10.008. Epub 2018 Oct 26.

Abstract

Although hematopoietic stem cell transplantation (HSCT) has been widely used in the treatment of many diseases, graft-versus-host disease (GVHD) remains a major complication after allogeneic HSCT. Butyrophilin-like 2 (BTNL2) protein has been reported to have the ability to inhibit T cell proliferation in vitro; its ability to inhibit T cell responses in vivo has not been determined. We show here that in vivo administration of recombinant BTNL2-IgG2a Fc (rBTNL2-Ig) fusion protein ameliorates GVHD in mice. This is related to the ability of rBTNL2-Ig to inhibit T cell proliferation, activation and Th1/Th17 cytokine production in vivo. Furthermore, rBTNL2-Ig treatment increases the generation of regulatory T cells. Our results suggest that rBTNL2-Ig has the potential to be used in the prevention and treatment of patients with GVHD.

Keywords: Activation; Butyrophilin-like 2; Graft-versus-host disease; Hematopoietic stem cell transplantation; Regulatory T cells; T cell proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Butyrophilins / immunology
  • Butyrophilins / metabolism*
  • Butyrophilins / pharmacology*
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacology
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Transplantation, Homologous

Substances

  • BTNL2 protein, human
  • BTNL2 protein, mouse
  • Butyrophilins
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Recombinant Fusion Proteins