title: Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease.
abstract: Chronic graft-versus-host disease (cGVHD) is an increasingly frequent complication of allogeneic stem cell transplantation. Current therapies for cGVHD reduce symptoms but are not cures. The B10.D2-->Balb/c (H-2(d)) minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD, was used in this study. We demonstrated that a single injection of an agonistic monoclonal antibody (mAb) against CD137, a member of the tumor necrosis factor receptor superfamily, reverses skin fibrosis, ulceration, and alopecia, a dominant feature of cGVHD (cutaneous GVHD), ultimately improving general health conditions. The reversal is associated with markedly reduced CD4(+) T-cell cytokines and increased apoptosis of donor CD4(+) T cells. The Fas pathway is required for ameliorating cutaneous GVHD by anti-CD137 mAb. Taken together, these data indicate that the anti-CD137 mAb has a therapeutic effect on cutaneous GVHD by removing donor CD4(+) T cells that cause cutaneous GVHD. Thus, our study demonstrates an agonistic mAb, specific for a costimulatory molecule, as a possible target for therapeutic intervention in cutaneous GVHD.
authors.affiliation: Department of Biological Science and Immunomodulation Reseach Center, University of Ulsan, Republic of Korea.
authors.forename: Juyang
authors.initials: J
authors.lastname: Kim
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Keunhee
authors.initials: K
authors.lastname: Park
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Hye-Jeong
authors.initials: HJ
authors.lastname: Choi
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Seok H
authors.initials: SH
authors.lastname: Nam
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous