慢性丙型肝炎患者Ⅰ型树突状细胞、淋巴细胞亚群的特点及临床意义

Characterization and clinical implication of peripheral monocyte-derived dendritic cells(DC1) and T lymphocyte subsets in patients with chronic hepatitis C

目的对慢性丙型肝炎患者Ⅰ型树突状细胞(dendritic cell1,DC1)、淋巴细胞亚群的免疫学特点进行研究。方法对18例慢性丙型肝炎患者及18名健康献血员外周血进行DC1分离、体外诱导培养及特异性DC1表面标志测定,同时对患者淋巴细胞亚群及各项生化指标和病毒载量进行检测,并对部分患者治疗前后的指标进行比较。结果体外培养可诱导出大量的DC1。表达于慢性丙型肝炎患者DC1表面的共刺激分子(CD80、CD86、CD1a)及MHC-Ⅱ类分子(HLA-DR)的水平均明显降低(患者分别为14.82%±13.32%、18.68%±13.76%、6.33%±4.98%和29.14%±14.00%;正常人分别为76.46%±12.25%、84.38%±9.72%、89.56%±8.96%和92.47%±9.34%),2组间差异有统计学意义(P<0.01);患者CD4+T淋巴细胞数量较正常对照组升高(P<0.001)、CD8+T淋巴细胞数量降低(P<0.01),CD4+/CD8+比值高于健康人(P<0.001),CD16+56+NK细胞低于健康人水平(P<0.01);慢性丙型肝炎患者ALT值与DC1数量、HBV DNA水平与DC1数量之间均存在负相关趋势;3例完成6个月α-干扰素治疗的患者,外周血单核细胞(PBMC)体外诱导培养产生的DC1数量均升高。结论慢性丙型肝炎患者DC1功能低下可能是HCV持续感染和免疫耐受的重要原因之一。HCV持续感染患者的淋巴细胞亚群发生变化,加重了丙型肝炎的慢性化。

Objective To explore immunologic characteristics of DC 1 and lymphocyte subsets in patients with chronic hepatitis C. Methods Eighteen patients with chronic hepatitis C and 18 healthy blood donors were enrolled in our study. DC1 was induced from peripheral blood mononuclear cells （PBMC） and surface markers of DC1 and lymphocytes subsets were detected by flow cytometry simultaneously. Biochemical parameters and HCV viral load were also recorded. Results A great number of DC1 were induced in vitro. Our data showed that fluorescence density of CD80, CD86, CDla and HLA-DR expression on DC1 was significantly lower in patients with chronic hepatitis C than that in normal controls （ 14.82% ± 13.32% vs 76.46% ±12.25%, 18.68% ± 13.76% vs 84.38% ± 9.72%, 6.33% ±4.98% vs 89.56% ± 8.96%, 29.14%± 14.00% vs 92.47% ± 9.34%, respectively, all P〈0.001 ）. We also found there was a significant increase in ratio and number of circulating CD4^＋ T lymphocyte subsets, and a decrease in CD8^＋ T cells and NK cells, which produced an increased ratio of CD4^＋ and CD8^＋ in the patient group compared with those in normal controls （ all P〈0.01 ）. The number of CD16^＋56^＋NK cells in the patient group was less than that in normal controls. In addition, we found a negative association of HCV RNA level with DC1 numbers as well as the serum ALT level and DC 1 numbers in patients with chronic hepatitis C. Furthermore, we analyzed 3 patients who were treated with IFN- a and found that the peripheral DC 1 production increased. Conclusions The decreased DC1 function may be one of the major reasons for continuous HCV infection and immunologic tolerance. The changes of lymphocyte subsets in patients with continuous HCV infection contribute to the progression of chronic hepatitis C.