Zhao Yang, Su Huiting, Shen Xiaofei, Du Junfeng, Zhang Xiaodong, Zhao Yong
Transplantation Biology Research Division, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beichen West Road 1-5, Chaoyang District, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, China.
Inflamm Res. 2017 Jul;66(7):571-578. doi: 10.1007/s00011-017-1032-8. Epub 2017 Mar 10.
CD52 (Campath-1 antigen), a glycoprotein of 12 amino acids anchored to glycosylphosphatidylinositol, is widely expressed on the cell surface of immune cells, such as mature lymphocytes, natural killer cells (NK), eosinophils, neutrophils, monocytes/macrophages, and dendritic cells (DCs). The anti-CD52 mAb, alemtuzumab, was used widely in clinics for the treatment of patients such as organ transplantation. In the present manuscript, we will briefly summarize the immunological function of CD52 and discuss the application of anti-CD52 mAb in transplantation settings.
We reviewed studies published until July 2016 to explore the role of CD52 in immune cell function and its implication in organ transplantation. We showed that ligation of cell surface CD52 molecules may offer costimulatory signals for T-cell activation and proliferation. However, soluble CD52 molecules will interact with the inhibitory sialic acid-binding immunoglobulin-like lectin 10 (Siglec10) to significantly inhibit T cell proliferation and activation. Although the physiological and pathological significances of CD52 molecules are still poorly understood, the anti-CD52 mAb, alemtuzumab, was used widely for the treatment of patients with chronic lymphocytic leukemia, autoimmune diseases as well as cell and organ transplantation in clinics.
Studies clearly showed that CD52 can modulate T-cell activation either by its intracellular signal pathways or by the interaction of soluble CD52 and Siglec-10 expressing on T cells. However, the regulatory functions of CD52 on other immune cell subpopulations in organ transplantation require to be studied in the near future.
CD52(坎帕泰1抗原)是一种由12个氨基酸组成的糖蛋白,通过糖基磷脂酰肌醇锚定在细胞表面,在免疫细胞如成熟淋巴细胞、自然杀伤细胞(NK)、嗜酸性粒细胞、中性粒细胞、单核细胞/巨噬细胞和树突状细胞(DC)的表面广泛表达。抗CD52单克隆抗体阿仑单抗在临床上广泛用于治疗器官移植等患者。在本手稿中,我们将简要总结CD52的免疫功能,并讨论抗CD52单克隆抗体在移植环境中的应用。
我们回顾了截至2016年7月发表的研究,以探讨CD52在免疫细胞功能中的作用及其在器官移植中的意义。我们发现细胞表面CD52分子的结合可能为T细胞活化和增殖提供共刺激信号。然而,可溶性CD52分子会与抑制性唾液酸结合免疫球蛋白样凝集素10(Siglec10)相互作用,从而显著抑制T细胞增殖和活化。尽管CD52分子的生理和病理意义仍知之甚少,但抗CD52单克隆抗体阿仑单抗在临床上广泛用于治疗慢性淋巴细胞白血病、自身免疫性疾病以及细胞和器官移植患者。
研究清楚地表明,CD52可以通过其细胞内信号通路或可溶性CD52与T细胞上表达的Siglec-10的相互作用来调节T细胞活化。然而,CD52在器官移植中对其他免疫细胞亚群的调节功能在不久的将来需要进一步研究。