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

Ryo Hatano, Kei Ohnuma, Junpei Yamamoto, Nam H. Dang, Taketo Yamada, Chikao Morimoto

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19 Citations (Scopus)

Abstract

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/γc-/- mice (hu-PBL-NOG mice), the mice exhibited the onset of GVHD symptoms associated with the presence of CD26high 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.

Original languageEnglish
Pages (from-to)263-277
Number of pages15
JournalBritish Journal of Haematology
Volume162
Issue number2
DOIs
Publication statusPublished - 2013 Jul 1

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Keywords

  • CD26 (DPP4)
  • Graft-versus-host disease
  • Haematopoietic stem cell transplantation
  • T cell costimulation

ASJC Scopus subject areas

  • Hematology

Cite this

Hatano, R., Ohnuma, K., Yamamoto, J., Dang, N. H., Yamada, T., & Morimoto, C. (2013). Prevention of acute graft-versus-host disease by humanized anti-CD26 monoclonal antibody. British Journal of Haematology, 162(2), 263-277. https://doi.org/10.1111/bjh.12378