CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells.
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).
Watanabe
Tomoko
T
Cellular Immunotherapy, Pharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., 3 Miyahara, Takasaki, Gunma 370-1295, Japan.
Masuyama
Jun-ichi
J
Sohma
Yoshiaki
Y
Inazawa
Hiroko
H
Horie
Kaori
K
Kojima
Kumiko
K
Uemura
Yasunori
Y
Aoki
Yumi
Y
Kaga
Shuji
S
Minota
Seiji
S
Tanaka
Toshiyuki
T
Yamaguchi
Yasunori
Y
Kobayashi
Tetsuto
T
Serizawa
Isao
I
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*
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