CD4＋ CD25＋调节性T细胞影响门脉高压症脾功能亢进患者免疫功能的机制

Effects of CD4 ＋ CD25 ＋ regulatory T cells on immune function of patients with portal hypertensioninduced hypersplenism

目的 探讨门脉高压症脾功能亢进患者CD4＋ CD25＋调节性T细胞（Treg）表达增高并影响脾脏免疫功能的机制.方法 门脉高压症脾功能亢进患者46例,对照组14例,采用流式细胞术检测脾脏及外周、脾静脉血中CD4＋ CD25＋ CD127low/ Treg和CD4＋T细胞、CD8＋T细胞,酶联免疫吸附试验（ELISA）法检测外周血转化生长因子（TGF）-β,白细胞介素（IL）-2、IL-4、IL-10,逆转录-聚合酶链反应（RT-PCR）检测脾脏中叉状头/翅膀状螺旋转录因子（Foxp3）的含量,并分析其相关性.结果 脾功能亢进组脾脏及脾静脉中CD4＋ CD25＋ CD127low/-Treg的表达较对照组显著增高[（13.0±2.6）％比（10.2±3.6）％,P＜0.05],脾脏中Foxp3含量增高（P＜0.05）,外周血中CD4＋T细胞、CD8＋T细胞及IL-2含量降低[（24.5±11.8）％、（21.9±8.1）％比（34.0 ±11.3） ng/L,P＜0.05],IL-10与TGF-β含量显著增高[（61.1 ±22.4）ng/L比（85.8 ±34.9） ng/L,P＜0.05],IL-4含量降低,但差异无统计学意义（P＞0.05）.外周血CD4＋ CD25＋ CD1271ow-Treg含量与CD4＋T细胞、CD8＋T细胞及IL-2含量呈显著负相关（P＜0.05）.结论 门脉高压症脾功能亢进患者CD4＋CD25＋ Treg表达显著增高,可能通过抑制CD4＋T和CD8＋T细胞的活化与增殖,促进细胞因子IL-10与TGF-β的分泌,参与了机体的免疫调节.

Objective To study the significance of the increased CD4 ＋ CD25 ＋ regulatory T cells （Treg） in patients with portal hypertension-induced hypersplenism,and their effects on the immune function.Methods The proportions of CD4 ＋ CD25 ＋ CD127low/-Treg in peripheral venous blood,splenic vein and spleen tissue were examined by uisng flow cytometry in 46 patients with portal hypertension-induced hypersplenism,and compared with those in 14 normal control samples.The expression of forkhead box P3 （Foxp3） in spleen tissue was detected by using reverse transcriptase-polymerase chain reaction （RT-PCR）.Enzyme linked immunosorbent assay （ELISA） was used to test the transforming growth factorβ （TGF-β）,interleukin （IL）-2,IL-4 and IL-10 in peripheral venous blood.Their correlation was analyzed.Results The expression levels of CD4 ＋ CD25 ＋ CD1271ow/-Treg in spleen tissue and splenic vein of hypersplenism group were significantly higher than in control group.The Foxp3 expression in spleen tissue was significantly enhanced,CD4 ＋ T,CD8 ＋ T and IL-2 levels in peripheral venous blood were significantly reduced,and IL-10 and TGF-β contents were significantly increased in hypersplenism groups than in control group （P＜0.05）.The contents of CD4＋ CD25＋ CD127low/-Treg and the levels of CD4＋ T cells,CD8 ＋ T cells and IL-2 showed a significantly negative correlation.Conclusion The expression of CD4 ＋CD25 ＋ Treg in patients with portal hypertension-induced hypersplenism is significantly increased,which may be involved in immune regulation by inhibiting the activation of CD4 ＋ T cells and CD8 ＋ T cells and decreasing the IL-2 level,and promoting the secretion of cytokines IL-10 and TGF-β.