title: CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells.
abstract: We previously reported that 4C8 monoclonal antibody (mAb) provides a costimulatory signal to human CD4+ T cells and consequently induces regulatory T (Treg) cells, which are hypo-responsive and suppress the polyclonal response of bystander CD4+ cells in a contact-dependent manner. In this study, we identified the antigen of 4C8 mAb as CD52. Costimulation with Campath-1H, a humanized anti-CD52 mAb, also induced Treg cells. Anti-CD52-induced Treg cells suppressed the proliferation of both CD4+ and CD8+ T cells provided with polyclonal or allogeneic stimulation. When Treg cells were induced from Staphylococcal enterotoxin B (SEB) treated cells, they suppressed the response to SEB more efficiently than that to another superantigen, SEA. Furthermore, anti-CD52-induced Treg cells could be expanded by culture with IL-2 followed by CD52-costimulation, and co-injection of expanded Treg cells suppressed lethal xenogeneic graft versus host disease (GvHD) reactions in SCID mice caused by human peripheral blood mononuclear cells (PBMCs).
authors.affiliation: Cellular Immunotherapy, Pharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., 3 Miyahara, Takasaki, Gunma 370-1295, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Masuyama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sohma
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inazawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Horie
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kojima
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Uemura
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aoki
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaga
authors.forename: Seiji
authors.initials: S
authors.lastname: Minota
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tetsuto
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Serizawa
mesh_terms: D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000074301:CD52 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: C465395:4C8 antigen, human; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006023:Glycoproteins; D007376:Interleukin-2; C031818:enterotoxin B, staphylococcal; D000074323:Alemtuzumab