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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2006-09, Vol.120 (3), p.247-259
• Main Authors: Watanabe, Tomoko, Masuyama, Jun-ichi, Sohma, Yoshiaki, Inazawa, Hiroko, Horie, Kaori, Kojima, Kumiko, Uemura, Yasunori, Aoki, Yumi, Kaga, Shuji, Minota, Seiji, Tanaka, Toshiyuki, Yamaguchi, Yasunori, Kobayashi, Tetsuto, Serizawa, Isao
• Format: Article
• Language: English
• Subjects: Alemtuzumab; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - immunology; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, Neoplasm - immunology; Biological and medical sciences; 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; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycoproteins - immunology; Graft vs Host Disease - immunology; Human; Humans; Immunopathology; Interleukin-2 - immunology; Lymphocyte Activation - immunology; Medical sciences; Mice; Mice, SCID; Regulatory T cells; Reverse Transcriptase Polymerase Chain Reaction; Suppressor T cells; T cells; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2006.05.006

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).