CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells |
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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 |
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Institution: | Cellular Immunotherapy, Pharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., 3 Miyahara, Takasaki, Gunma 370-1295, Japan. |
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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). |
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Keywords: | Human T cells Regulatory T cells Suppressor T cells |
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