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Prevention of acute graft‐versus‐host disease by humanized anti‐ CD 26 monoclonal antibody
Author(s) -
Hatano Ryo,
Ohnuma Kei,
Yamamoto Junpei,
Dang Nam H.,
Yamada Taketo,
Morimoto Chikao
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12378
Subject(s) - immunology , medicine , monoclonal antibody , graft versus host disease , antibody , humanized mouse , peripheral blood mononuclear cell , t cell , monoclonal , transplantation , immune system , in vitro , biology , biochemistry
Summary CD 26 ( DPP 4) is a T cell costimulatory molecule as well as T cell activation marker, and CD 26 + T cells are accumulated in inflamed tissues, such as rheumatoid synovitis and autoimmune thyroiditis. In the present study, we found accumulation of CD 26 + T cells in graft‐versus‐host disease ( GVHD ) target organs. To expand our in vitro findings to an in vivo system, we examined CD 26‐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 CD 26 high human lymphocytes in the peripheral blood and GVHD target tissues. Administration of humanized anti‐human CD 26 monoclonal antibody ( mA b) decreased x‐ GVHD severity and prolonged survival in hu‐ PBL ‐ NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA 4‐ immunoglobulin fusion protein diminished engraftment of human lymphocytes. Importantly, anti‐ CD 26 mA b treatment preserved the graft‐versus‐leukaemia effects in studies using cotransplantation of P 815 murine leukaemic cells. In addition, CD 26 + lymphocytes infiltrated the GVHD patients' target tissues. Altogether, our data indicate a role for CD 26 in the regulation of GVHD and point to CD 26 as a novel target for therapeutic intervention in this disease.