Brett S, Baxter G, Cooper H, Johnston J M, Tite J, Rapson N
Biology Division, Wellcome Research Laboratories, Beckenham, Kent, UK.
Immunology. 1996 May;88(1):13-9. doi: 10.1046/j.1365-2567.1996.d01-650.x.
Patients with severe rheumatoid arthritis who had failed treatment with conventional therapies were treated with a course of five or 10 daily intravenous infusions of CAMPATH-1H, a humanized antibody against the CD52 antigen, resulting in profound depletion of peripheral blood mononuclear cells. During the subsequent 18 months, lymphocytes were analysed for sub-populations by fluorescence-activated cell sorter (FACS) and for proliferation in response to polyclonal T-cell stimulation with anti-CD3 or staphylococcal enterotoxin B (SEB). Treatment resulted in almost complete depletion of lymphocytes from the blood followed by gradual repopulation. CD16+ natural killer (NK) cells and CD14+ monocytes returned to pretreatment levels within 1-2 months. CD19+ B cells returned to within 50% of pre-treatment levels by day 66 and to within normal range by day 150, whereas CD8+ T cells recovered to 50% of pretreatment levels by day 66, but did not show any further increase during the rest of the study period. The most profound effects were on the CD4+ T lymphocyte sub-population, as the mean CD4+ count did not increase above 20% of pre-treatment level at any time during the study period (550 days), at all the doses tested. The T cells which initially repopulated the blood 1-2 months after treatment, nearly all expressed the activation markers human leucocyte antigen (HLA)-DR and CD45RO, although the percentage of T cells expressing these molecules gradually declined to normal levels over time. Proliferative responses to polyclonal T-cell stimulation (anti-CD3 and SEB) were also significantly reduced in the first few months after treatment, but recovered to pre-treatment levels by day 250. The relationship between these observations and the clinical response is discussed.
对常规治疗无效的重度类风湿性关节炎患者，给予一个疗程（每日一次，共5次或10次）静脉输注CAMPATH - 1H（一种抗CD52抗原的人源化抗体）治疗，导致外周血单核细胞显著减少。在随后的18个月里，通过荧光激活细胞分选仪（FACS）分析淋巴细胞亚群，并检测其对用抗CD3或葡萄球菌肠毒素B（SEB）进行多克隆T细胞刺激的增殖反应。治疗导致血液中淋巴细胞几乎完全耗竭，随后逐渐重新填充。CD16⁺自然杀伤（NK）细胞和CD14⁺单核细胞在1 - 2个月内恢复到治疗前水平。CD19⁺B细胞在第66天恢复到治疗前水平的50%以内，并在第150天恢复到正常范围内，而CD8⁺T细胞在第66天恢复到治疗前水平的50%，但在研究期的其余时间内未显示进一步增加。最显著的影响是对CD4⁺T淋巴细胞亚群，因为在研究期（550天）内的任何时间，在所有测试剂量下，平均CD4⁺计数均未增加到高于治疗前水平的20%。治疗后1 - 2个月最初重新填充血液的T细胞，几乎都表达激活标志物人类白细胞抗原（HLA）- DR和CD45RO，尽管随着时间的推移，表达这些分子的T细胞百分比逐渐下降至正常水平。治疗后的头几个月，对多克隆T细胞刺激（抗CD3和SEB）的增殖反应也显著降低，但在第250天恢复到治疗前水平。讨论了这些观察结果与临床反应之间的关系。
