Brett S J, Baxter G, Cooper H, Rowan W, Regan T, Tite J, Rapson N
Molecular Immunology Group, Wellcome Research Laboratories, Kent, UK.
Int Immunol. 1996 Mar;8(3):325-34. doi: 10.1093/intimm/8.3.325.
CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expressed at high levels on normal T and B lymphocytes and at lower levels on monocytes, while being absent on granulocytes and bone marrow stem cell precursors. The emergence of CD52- lymphocytes of both T and B cell lineages was observed in three out of 25 rheumatoid arthritis patients treated with teh humanized antibody Campath-1H in phase II clinical trial. Whereas the majority of CD52- B cells had disappeared from the peripheral blood by 3 months post-treatment, both CD52- CD4+ and CD8+ T cells persisted in the circulation for at least 20 months. In the two patients that were tested, the GPI-anchored surface molecules CD55 and CD59 were also absent on the CD52- cells, although expression of other cell surface transmembrane, proteins (CD3, CD4 and CD2) was unaffected. The CD52- cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture. Both CD52- and C52+ clones, established from one of the patients, responded to a similar extent to several T cell mitogens, as assessed by proliferation, suggesting that a general defect in expression of GPI-linked molecules does not impair T cell activation. These data show that an immune attack against a GPI-anchored surface molecule can result in the selection of a GPI-anchor-deficient cell population. Despite the persistence of CD52- T cells in the peripheral blood, no adverse reactions associated with the presence of these cells were noted in any of the patients; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.
CD52是一种糖基磷脂酰肌醇（GPI）连接的糖蛋白，在正常T和B淋巴细胞上高水平表达，在单核细胞上低水平表达，而在粒细胞和骨髓干细胞前体上不表达。在一项II期临床试验中，接受人源化抗体Campath-1H治疗的25例类风湿性关节炎患者中有3例出现了T和B细胞系的CD52阴性淋巴细胞。虽然大多数CD52阴性B细胞在治疗后3个月从外周血中消失，但CD52阴性的CD4 +和CD8 + T细胞在循环中持续存在至少20个月。在接受检测的两名患者中，CD52阴性细胞上也不存在GPI锚定的表面分子CD55和CD59，尽管其他细胞表面跨膜蛋白（CD3、CD4和CD2）的表达未受影响。尽管在培养中反复重新刺激，CD52阴性细胞在体外仍保持稳定的表型。从其中一名患者建立的CD52阴性和CD52阳性克隆对几种T细胞有丝分裂原的反应程度相似，通过增殖评估表明，GPI连接分子表达的普遍缺陷不会损害T细胞活化。这些数据表明，针对GPI锚定表面分子的免疫攻击可导致选择GPI锚定缺陷的细胞群体。尽管CD52阴性T细胞在外周血中持续存在，但在任何患者中均未观察到与这些细胞存在相关的不良反应；事实上，与试验中的其他患者相比，他们在接受Campath-1H治疗后缓解时间更长。
