Vinay D S, Kwon B S
Indiana University School of Medicine, and the Walther Oncology Center, 635 Barnhill Drive, Indianapolis, IN, 46202-5120, USA.
Semin Immunol. 1998 Dec;10(6):481-9. doi: 10.1006/smim.1998.0157.
4-1BB is an inducible T cell surface receptor which belongs to the tumor necrosis factor receptor superfamily, a group of cysteine-rich cell-surface molecules. Both human and mouse 4-1BB recently received HLDA nomenclature. Naive T cells lack 4-1BB, which is not only induced upon T cell activation, but also remains on activated T cells. The natural ligand for 4-1BB, 4-1BBL is also induced and is found on activated antigen-presenting cells. Cross-linking of the 4-1BB molecule by agonistic antibody transmits a distinct and potent co-stimulatory signal leading to the activation and differentiation of CD4(+) and CD8(+) cells. 4-1BB transmits signals through the TRAF2-NIK pathway and activates NF-kappaB. Signals relayed through 4-1BB inhibit activation-induced cell death and rescue the immune system during the post-CD28 phase. Antibodies to the 4-1BB molecule can increase GVHD, accelerate the rejection of cardiac allograft and skin transplants, and eradicate established tumors. Interference with the 4-1BB-4-1BBL pathway may be of therapeutic use in the treatment of HIV infection. 4-1BB-deficient mice show dysregulated immune responses and mount elevated Ig responses to T-dependent antigens.
4-1BB是一种可诱导的T细胞表面受体，属于肿瘤坏死因子受体超家族，该家族是一组富含半胱氨酸的细胞表面分子。人和小鼠的4-1BB最近都获得了HLDA命名。初始T细胞缺乏4-1BB，4-1BB不仅在T细胞活化时被诱导，而且在活化的T细胞上持续存在。4-1BB的天然配体4-1BBL也被诱导，并在活化的抗原呈递细胞上发现。激动性抗体使4-1BB分子交联可传递独特而有效的共刺激信号，导致CD4(+)和CD8(+)细胞活化和分化。4-1BB通过TRAF2-NIK途径传递信号并激活NF-κB。通过4-1BB传递的信号可抑制活化诱导的细胞死亡，并在CD28后阶段拯救免疫系统。针对4-1BB分子的抗体可增加移植物抗宿主病，加速心脏同种异体移植和皮肤移植的排斥反应，并根除已形成的肿瘤。干扰4-1BB-4-1BBL途径可能在治疗HIV感染中具有治疗用途。4-1BB缺陷小鼠表现出免疫反应失调，对T细胞依赖性抗原的Ig反应升高。
