Prevention of acute graft-versus-host disease by humanized anti-CD26 monoclonal antibody

Br J Haematol. 2013 Jul;162(2):263-77. doi: 10.1111/bjh.12378. Epub 2013 May 21.


CD26 (DPP4) is a T cell costimulatory molecule as well as T cell activation marker, and CD26(+) T cells are accumulated in inflamed tissues, such as rheumatoid synovitis and autoimmune thyroiditis. In the present study, we found accumulation of CD26(+) T cells in graft-versus-host disease (GVHD) target organs. To expand our in vitro findings to an in vivo system, we examined CD26-dependent organ injury in a xenogeneic GVHD (x-GVHD) murine model. Following intraperitoneal injection of human peripheral blood mononuclear cells into non-obese diabetic severe combined immunodeficiency/γ(c) (-/-) mice (hu-PBL-NOG mice), the mice exhibited the onset of GVHD symptoms associated with the presence of CD26(high) human lymphocytes in the peripheral blood and GVHD target tissues. Administration of humanized anti-human CD26 monoclonal antibody (mAb) decreased x-GVHD severity and prolonged survival in hu-PBL-NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA4- immunoglobulin fusion protein diminished engraftment of human lymphocytes. Importantly, anti-CD26 mAb treatment preserved the graft-versus-leukaemia effects in studies using cotransplantation of P815 murine leukaemic cells. In addition, CD26(+) lymphocytes infiltrated the GVHD patients' target tissues. Altogether, our data indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.

Keywords: CD26 (DPP4); T cell costimulation; graft-versus-host disease; haematopoietic stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Dipeptidyl Peptidase 4 / immunology*
  • Disease Models, Animal
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal, Humanized
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4