树突状细胞的非特异性免疫功能降低对HBV、HCV清除及细胞毒性T淋巴细胞应答无影响  

Impaired non-viral specific immune function of dendritic cell does not interfere with clearance and cyto-toxic T lymphocyte response to HBV or HCV

作　　者：范春蕾[1] 陈红松[1] 李若冰[1] 王松霞[1] 从旭[1] 费然[1] 蒋栋[1] 王宇[1] 魏来[1] 

机构地区：[1]北京大学人民医院,北京大学肝病研究所,北京100044

出　　处：《中华肝脏病杂志》2004年第2期67-71,共5页Chinese Journal of Hepatology

基　　金：国家自然科学基金(30170844);国家十五科技攻关计划(2001BA705B06);国家973计划(G1999054106)

摘　　要：目的 观察HBV、HCV感染者树突状细胞(DC)的非病毒特异性免疫功能状态与细胞毒性T淋巴细胞(CTL)免疫应答以及病毒清除的关系。方法 对25例成人慢性HBV和HCV合并感染者进行了间隔8年的两次调查,依据临床转归分为HBV和HCV均清除组(A组)14例,单独HCV清除者(B组)6例,单独HBV清除者(C组)3例,HBV和HCV均未清除者(D组)2例,对照组(N组)为同一地区健康献血员11例。体外分离培养D C,检测其表型及抗原摄取功能、刺激异体淋巴细胞增殖能力和4组感染者的CTL免疫应答情况。 结果 B、C、D组与A组、N组比较,DC的非病毒特异性免疫功能降低,表现为CD86表达的降低、刺激异体淋巴细胞增殖的能力下降以及抗原摄取能力降低。A组对HBV和HCV的4条抗原表位多肽均有较高的CTL应答率(12/12);B组对HCV的两条抗原表位多肽均有应答(5/5),但无对HBV两条表位多肽均应答者,仅有1例对P2有反应;C组对HBV的抗原表位多肽均有应答,但无对两条HCV表位多肽均应答者;D组及N组对HBV或HCV所有实验多肽均无应答。 结论 HBV和HCV的清除与病毒特异性的CTL应答相关。HBV和(或)HCV持续存在可能是导致DC功能异常的原因。Objective To investigate the correlation between impaired non-viral specific immune function of dendritic cell (DC) and viral clearance and cytotoxic T lymphocyte (CTL) response to HBV or HCV in patients with HBV and HCV coinfection. Methods Twenty-five patients with HBV and HCV coinfection were investigated in this study. In 1994 and 2002, biochemical and virological markers and quantitative serum HBV DNA and HCV RNA levels were detected in these patients. According to the virus clearance status, these patients were divided into 4 groups: 14 patients with both HBV and HCV clearance (Group A), 6 patients with HCV clearance only (Group B), 3 patients with HBV clearance only (Group C), and 2 patients with persistent infection of HBV and HCV (Group D). Phenotypes and immune functions of monocyte-derived DCs were compared between these groups. 51Cr release assay were used to measure CTL response to epitopes derived from HBV, HCV or influenza virus (as positive control) in HLA-A2+ patients. Results Impaired non-viral specific immune functions of DCs were observed in group B, C and D compared with group A and normal donors (Group N). These impaired functions included CD86 decreasing expression and lower capacity to stimulating allogenic T cells and uptaking antigen. The specific CTL response to HBV- and HCV-derived peptides could be induced in group A (12/12). The specific CTL response to HBV-derived peptides or to HCV-derived peptides could be induced in group C (3/3) or B (5/5), respectively. But the specific CTL response to both of two HBV-derived peptides or two HCV-derived peptides could not be induced in group C (0/3) or B (0/5), respectively. And no CTL response to HBV or HCV- derived peptides could be induced in groups D (0/1) and N (0/4). Conclusion 1. The results suggest that specific CTL response to HBV or HCV play a vital role in the viral clearance. 2. The DCs with impaired non-viral specific immune functions exist in chronic patients with HBV and/or HCV infection, but do not interfere with clearance and C

关 键 词：树突状细胞 非特异性免疫功能降低 HBV HCV 细胞毒性 T淋巴细胞 免疫应答 乙型肝炎病毒 丙型肝炎病毒 

分 类 号：R512.6[医药卫生—内科学] R392[医药卫生—临床医学]