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
Cellular Immunotherapy, Pharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co. Ltd., 3 Miyahara, Takasaki, Gunma 370-1295, Japan.
Clin Immunol. 2006 Sep;120(3):247-59. doi: 10.1016/j.clim.2006.05.006. Epub 2006 Jun 22.
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).
我们之前报道过，4C8单克隆抗体（mAb）可向人CD4+ T细胞提供共刺激信号，从而诱导调节性T（Treg）细胞，这些细胞反应低下，并以接触依赖的方式抑制旁观者CD4+细胞的多克隆反应。在本研究中，我们鉴定出4C8 mAb的抗原为CD52。用一种人源化抗CD52 mAb——Campath-1H进行共刺激，也可诱导Treg细胞。抗CD52诱导的Treg细胞抑制了接受多克隆或同种异体刺激的CD4+和CD8+ T细胞的增殖。当从经葡萄球菌肠毒素B（SEB）处理的细胞中诱导出Treg细胞时，它们对SEB的反应抑制作用比对另一种超抗原SEA的抑制作用更有效。此外，抗CD52诱导的Treg细胞可通过用IL-2培养然后进行CD52共刺激来扩增，并且共同注射扩增后的Treg细胞可抑制由人外周血单个核细胞（PBMC）引起的SCID小鼠致死性异种移植物抗宿主病（GvHD）反应。
