Prevention of acute graft‐versus‐host disease by humanized anti‐CD26 monoclonal antibody |
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Authors: | Ryo Hatano Kei Ohnuma Junpei Yamamoto Nam H. Dang Taketo Yamada Chikao Morimoto |
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Affiliation: | 1. Department of Therapy Development and Innovation for Immune disorders and Cancers, Graduate School of Medicine, Juntendo University, , Tokyo, Japan;2. Division of Hematology/Oncology, University of Florida, , Gainesville, FL, USA;3. Department of Pathology, Keio University School of Medicine, , Tokyo, Japan |
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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. |
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Keywords: | CD26 (DPP4) graft‐versus‐host disease T cell costimulation haematopoietic stem cell transplantation |
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