Horneff G, Emmrich F, Reiter C, Kalden J R, Burmester G R
Max Planck Clinical Research Group, Department of Medicine III, University of Erlangen-Nuremberg, Germany.
J Rheumatol. 1992 Dec;19(12):1845-50.
A 49-year-old patient with refractory rheumatoid arthritis was treated repeatedly with anti-CD4 murine monoclonal antibodies. While the first anti-CD4 treatment resulted in a marked, however transient, depletion of CD4+ cells from 1070 to a minimum of 175/microliters, a second treatment cycle resulted in a persistent decrease. Despite this marked depletion, no major clinical improvement occurred, which was in striking contrast to other patients treated in a similar way. Of interest, the administration of low doses of chlorambucil led to significant clinical benefits. Markedly reduced numbers of CD4+ cells (200-500/microliters) were observed for more than 2 years, while the numbers of CD8+ cells increased after the second treatment. No infectious episodes occurred. Discontinuation of chlorambucil did not lead to increasing amounts of CD4+ cells. In contrast to the rapid reduction of CD4+ cells from the blood stream induced by anti-CD4 infusions, there was a considerable delay until altered CD4/CD8 ratios were observed in intraarticular sites. No evidence was found for either humoral or cellular immune reactivities towards CD4+ T helper cells. Our findings suggest that in certain patients undergoing anti-CD4 therapy there may be a reduced capacity of the CD4+ T helper cell pool to regenerate.
一名49岁的难治性类风湿关节炎患者多次接受抗CD4鼠单克隆抗体治疗。首次抗CD4治疗导致CD4+细胞显著但短暂地从1070降至最低175/微升，而第二个治疗周期导致持续下降。尽管CD4+细胞显著减少，但并未出现明显的临床改善，这与以类似方式治疗的其他患者形成鲜明对比。有趣的是，给予低剂量苯丁酸氮芥带来了显著的临床益处。超过2年观察到CD4+细胞数量显著减少（200 - 500/微升），而第二次治疗后CD8+细胞数量增加。未发生感染事件。停用苯丁酸氮芥并未导致CD4+细胞数量增加。与抗CD4输注引起的血流中CD4+细胞迅速减少相反，关节内部位观察到CD4/CD8比值改变存在相当长的延迟。未发现针对CD4+辅助性T细胞的体液或细胞免疫反应性证据。我们的研究结果表明，在某些接受抗CD4治疗的患者中，CD4+辅助性T细胞池的再生能力可能降低。
