天疱疮患者外周血CD4＋T细胞活化状态及其表面共刺激分子的表达

Activation state of and expressions of surface co-stimulatory molecules on peripheral CD4＋ T cells frompatients with pemphigus

目的探讨天疱疮患者和健康人外周血CD4＋T细胞的活化状态及其表面共刺激分子的表达情况。方法收集天疱疮患者90例，其中初发24例，稳定期51例，复发期15例；健康对照30例。运用流式细胞仪检测天疱疮患者外周血CD4＋T细胞的活化标志CD69及其表面共刺激分子，包括细胞间黏附分子-1（ICAM-1）、诱导性协同刺激分子（ICOS）、CD40配体（CD40L）和OX40的表达情况，并和健康对照组进行比较。用Graphpad5．0软件进行统计分析，两组间比较采用非参数（Mann—Whitneytest）检验。结果天疱疮患者外周血CD4＋T细胞表面CD69表达比例为（2．46±0．19）％，显著高于健康对照组[（1．26±0．19）％，P〈0．01]，且初发、稳定期和复发期天疱疮患者CD4＋T细胞表面CD69的表达均显著高于健康对照组（P〈0．01），但不同病期患者间差异无统计学意义。天疱疮患者CD4＋T细胞表面ICAM-1、CD40L和OX40的表达比例分别为（55．88±1．67）％、（2．23±0．22）％和（2．55±0．29）％，分别显著高于健康对照组[（47．75±2．52）％、（0．73±0．07）％和（0．62±0．17）％，P〈0．05或0．01]，但在初发、稳定期和复发期患者之间差异无统计学意义；ICOS的表达在初发患者中显著高于健康对照组，分别为（3．73±0．60）％和（2．39±0．16）％（P〈0．05）。结论天疱疮患者外周血CD4＋T细胞处于相对活化的状态，其表面的共刺激分子也呈高表达，表明CD4＋T细胞可能通过高表达的共刺激分子和B细胞相互作用，参与疾病的发生和发展。

Objective To investigate the activation state of and expressions of surface co-stimulatory molecules on peripheral CD4＋ T ceils from patients with pemphigus and healthy human controls. Methods Ninety patients with pemphigus including 24 patients with first-onset pemphigus, 51 with quiescent pemphigus and 15 with recurrent pemphigus, as well as 30 healthy human controls were enrolled in this study. Peripheral blood samples were obtained from these subjects followed by lymphocyte isolation. Flow cytometry was performed to detect the expressions of CD69, intercellular adhesion molecule-1 （ICAM-1）, inducible co-stimulatory molecule （ICOS）, CD40 ligand （CD40L） and OX40 on CD4＋ T cells. Statistical analysis was done by Mann-Whitney test using Graphpad 5.0 software. Results The expression rate of CD69 on peripheral CD4＋ T cells from the healthy human controls was significantly lower than that from patients with pemphigns, patients with first-onset pemphigus, patients with quiescent pemphigus, and patients with recurrent pemphigus （（1.26 ± 0.19）% vs. （2.46 ± 0.19）%, （2.77 ± 0.40）%, （2.15 ± 0.25）% and （2.36 ± 0.35）%, all P 〈 0.05）. The patients with pemphigus also showed a significant increase in the expression rates of ICAM-1, CD40L and OX40 compared with the healthy human controls （（55.88 ± 1.67）% vs. （47.75 ± 2.52）%, P〈 0.05; （2.23 ± 0.22）% vs. （0.73 ± 0.07）%, P〈 0.01; （2.55 ±0.29）% vs. （0.62 ± 0.17）%, P 〈 0.01 ）. No significant differences were observed between patients with different stages of pemphigus in the expression rates of CD69, ICAM-1, CD40L or OX40 （all P 〉 0.05）. The percentage of ICOS- expressing CD4＋ T cells was significantly up-regulated in only patients with first-onset pemphigus as compared to the healthy controls （（3.73 ± 0.60）% vs. （2.39 ± 0.16）%, P 〈 0.05）. Conclusions The peripheral blood CD4＋ T cells from patients with pemphigus are in a relatively active state with up-regulated surface expressions of many co- stimulatory molecules, suggesting that CD4＋ T cells are involved in the initiation and progression of pemphigus by interacting with B cells through co-stimulatory molecules.