慢性乙型肝炎患者在HBV不同抗原负载下树突状细胞功能的变化

目的观察在不同HBV抗原负载下树突状细胞(DC)功能的变化及在核苷(酸)类药物抗病毒治疗后DC的功能变化。方法分离17例慢性乙型肝炎患者外周血单个核细胞(PBMC),并在不同抗原负载下(HBsAg、HBcAg、HBsAg联合HBcAg)诱导DC分化成熟,用流式细胞技术测定DC表面共刺激分子CD80、CD83、CD1a及HLA-Ⅱ类分子HLA-DR表达水平,同时用淋巴细胞增殖试验评估DC功能。结果与负载HBsAg诱导相比,HBcAg、HBsAg联合HBcAg诱导下DC共刺激分子表达明显增强(HLA-DR:85.12±1.55比98.37±1.27比99.21±1.33;CD1a:15.69±2.46比16.25±2.33比42.20±1.10;CD80:71.88±6.38比80.74±3.23比94.70±2.77;CD83:32.64±2.77比42.55±2.88比44.16±1.89)。淋巴细胞增殖试验提示DC功能改善更显著,尤其HBsAg联合HBcAg诱导DC功能改善更加明显(HBV DNA阳性:7.29±0.17比7.99±0.43比8.56±0.31;HBV DNA阴性:7.48±0.30比8.22±0.41比8.78±0.31)。将17例慢性乙型肝炎患者在核苷(酸)类药物抗病毒治疗前后DC功能进行比较,经抗病毒治疗在充分抑制HBV DNA复制的情况下,DC功能的恢复更趋于完善(HLA-DR:99.21±1.33比99.82±2.67;CD1a:42.20±1.10比71.33±5.89;CD80:94.70±2.77比96.42±3.56;CD83:44.16±1.89比68.34±2.11)。结论 HBsAg联合HBcAg诱导DC细胞功能明显得到恢复和增强,HBV DNA阴性时诱导自体DC功能恢复更趋完善。

Functional status of dendritic cells induced by different hepatitis B virus antigen in chronic hepatitis B patients

Objective To investigate the functional changes of dendritic cells (DC) from chronic hepatitis B (CHB) patients upon stimulation of different hepatitis B virus antigen and treated with antiviral drugs.Methods Monocytes, isolated from peripheral blood mononuclear cells (PBMC) in 17 CHB patients, were induced into mature DC with hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), and HBcAg combination with HBsAg, respectively.Co-stimulatory molecules on DC surface, including CD1a, CD80, CD83 and human leukocyte antigen DR (HLA-DR), were analyzed using flow cytometry.The functions of DC were evaluated using allogeneic mixed lymphocyte reaction assay.Results Compared with those in HBsAg-induced DC, levels of CD1a, CD80, CD83 and HLA-DR were higher on DC induced by HBcAg alone, as well as HBsAg combination with HBcAg (HLA-DR: 85.12±1.55 vs.98.37±1.27 vs.99.21±1.33;CD1a: 15.69±2.46 vs.16.25±2.33 vs.42.20±1.10;CD80: 71.88±6.38 vs.80.74±3.23 vs.94.70±2.77;CD83: 32.64±2.77 vs.42.55±2.88 vs.44.16±1.89).The mixed lymphocyte reaction ability of DC showed the similar pattern (HBV DNA+: 7.29±0.17 vs.7.99±0.43 vs.8.56±0.31;HBV DNA-: 7.48±0.30 vs.8.22±0.41 vs.8.78±0.31).After anti-viral therapy, functional status of DC, such as co-stimulatory molecules expression and the mixed lymphocyte reaction ability, were improved more obviously than those at baseline (HLA-DR:99.21±1.33 vs.99.82±2.67;CD1a:42.20±1.10 vs.71.33±5.89;CD80:94.70±2.77 vs.96.42±3.56;CD83:44.16±1.89 vs.68.34±2.11).Conclusion The dysfunction of DC as the important phagocytes from CHB patients might be improved and recovered through combined induction with HBsAg and HBcAg, which could be further relived after anti-viral therapy.It provides a effective and potential therapy for CHB.