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目的:探讨四氯化碳诱导肝纤维化小鼠滤泡辅助性T细胞(follicular helper cells，Tfh)中可诱导共刺激分子(inducible costimulator，ICOS)的表达及ICOS阻断剂对白细胞介素(interleukin，IL)-21表达的影响。方法:模型组(四氯化碳致肝纤维化组)与正常组BALB/c小鼠各40只，流式细胞仪分析测定不同阶段Tfh细胞的动态表达、Tfh细胞中ICOS的表达趋势及特征以及ICOS阻断剂处理后肝纤维化小鼠脾淋巴细胞中Tfh的IL-21的分泌水平。结果:与正常组(0 W)CD4n ＋ T细胞中Tfh细胞群的比例相比，模型组CD4n ＋CXCR5n ＋ Tfh细胞群的比例逐渐上调，13 W达到峰值，20 W虽有所下调但仍保持较高水平[0 W：(7.52±2.30)%，8 W：(20.45±4.16)%，13 W：(27.83±5.51)%，20 W：(22.97±4.71)%]，差异有统计学意义(n t值分别为8.56、9.62和8.34，n P值均<0.05)。随着病程的进展，与正常组(0 W)相比，肝纤维化小鼠Tfh细胞群ICOS的表达水平逐渐上调，13 W达到峰值，20 W虽有所下调但仍保持较高水平[0 W：(6.45±2.04)%，8 W：(19.81±4.51)%，13 W：(41.20±7.17)%，20 W：(32.53±5.01)%]，差异有统计学意义(n t值分别为7.63、13.19、13.64，n P值均<0.05)。在13 W，用流式细胞术检测Tfh细胞群IL-21的表达水平，结果显示，与ICOS阻断剂非处理组相比，ICOS阻断剂处理组Tfh细胞群IL-21的表达水平显著下调，差异有统计学意义[(8.89±3.92)%比(0.03±0.02)%，n t＝6.40，n P<0.05]。n 结论:肝纤维化小鼠Tfh细胞的数量和ICOS的表达显著上调，ICOS阻断剂可抑制Tfh细胞分泌IL-21，提示ICOS可能通过Tfh细胞调控肝纤维化的发生发展。“,”Objective:To explore the expression of inducible costimulator (ICOS) in follicular helper T cells(Tfh) and effect of ICOS blocker on the expression of interleukin (IL)-21 in mice of liver fibrosis induced by carbon tetrachloride.Methods:There were 40 BALB/c mice for model group and 40 BALB/c mice for control group. The expression trends and characteristics of different periods of Tfh cell and ICOS on the Tfh cell were detected by flow cytometric analysis. The IL-21 level in Tfh cell was also analysed after using ICOS blocker in 13 weeks.Results:The expression of Tfh cell and ICOS were gradually increased. Compared with the proportion of Tfh cells in CD4n + T cells[control group (0 W)], the proportion of CD4n + CXCR5n + Tfh cells in model group was gradually increased, and reached the peak at 13 weeks, then decreased at 20 weeks, but still maintained a high level[0 W: (7.52±2.30)%, 8 W: (20.45±4.16)%, 13 W: (27.83±5.51)%, 20 W: (22.97±4.71)% ]. Compared to control group(0 W), model group showed significantly higher expression of Tfh cell(n t values were 8.56, 9.62 and 8.34 respectively, all n P values <0.05). The same trends were also founded in the expression of ICOS in Tfh cell group [(0 W: (6.45±2.04)%, 8 W: (19.81±4.51)%, 13 W: 41.20±7.17%, 20 W: (32.53±5.01)%]. The statistically significant differences also have been found between the groups( n t values were 7.63, 13.19 and 13.64, respectively, all n P values <0.05). At 13 weeks, the expression level of IL-21 in Tfh cell group was detected by flow cytometry. The results showed that compared with the control group, the expression level of IL-21 in the ICOS antagonist treated group was significantly decreased[(8.89±3.92)% vs (0.03±0.02)%, n t=6.40, n P<0.05].n Conclusion:The number of Tfh cells and the expression of ICOS were significantly up-regulated in mice with hepatic fibrosis. ICOS blocker could inhibit IL-21 secretion of Tfh cells, suggesting that ICOS may regulate the occurrence and development of liver fibrosis through Tfh cells.