title: Prevention of acute graft-versus-host disease by humanized anti-CD26 monoclonal antibody.
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/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.
authors.affiliation: Department of Therapy Development and Innovation for Immune disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
authors.forename: Junpei
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: CD26 (DPP4); T cell costimulation; graft-versus-host disease; haematopoietic stem cell transplantation