CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells

Tomoko Watanabe; Jun-ichi Masuyama; Yoshiaki Sohma; Hiroko Inazawa; Kaori Horie; Kumiko Kojima; Yasunori Uemura; Yumi Aoki; Shuji Kaga; Seiji Minota; Toshiyuki Tanaka; Yasunori Yamaguchi; Tetsuto Kobayashi; Isao Serizawa

doi:10.1016/j.clim.2006.05.006

CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells

Clin Immunol. 2006 Sep;120(3):247-59. doi: 10.1016/j.clim.2006.05.006. Epub 2006 Jun 22.

Authors

Tomoko Watanabe¹, Jun-ichi Masuyama, Yoshiaki Sohma, Hiroko Inazawa, Kaori Horie, Kumiko Kojima, Yasunori Uemura, Yumi Aoki, Shuji Kaga, Seiji Minota, Toshiyuki Tanaka, Yasunori Yamaguchi, Tetsuto Kobayashi, Isao Serizawa

Affiliation

¹ Cellular Immunotherapy, Pharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., 3 Miyahara, Takasaki, Gunma 370-1295, Japan.

PMID: 16797237
DOI: 10.1016/j.clim.2006.05.006

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).

MeSH terms

Alemtuzumab
Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal, Humanized
Antibodies, Neoplasm / immunology
Antigens, CD / biosynthesis
Antigens, CD / immunology*
Antigens, Neoplasm / immunology*
CD52 Antigen
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology
Enterotoxins / immunology
Epitopes, T-Lymphocyte / immunology
Female
Forkhead Transcription Factors / biosynthesis
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / immunology
Glycoproteins / immunology*
Graft vs Host Disease / immunology
Humans
Interleukin-2 / immunology
Lymphocyte Activation / immunology
Mice
Mice, SCID
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / immunology*

Substances

4C8 antigen, human
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antibodies, Neoplasm
Antigens, CD
Antigens, Neoplasm
CD52 Antigen
CD52 protein, human
Enterotoxins
Epitopes, T-Lymphocyte
FOXP3 protein, human
Forkhead Transcription Factors
Glycoproteins
Interleukin-2
enterotoxin B, staphylococcal
Alemtuzumab