慢加急性肝衰竭患者树突状细胞频率、表型、功能变化  

Decreased numbers and impaired function of dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure

作　　者：李宁[1] 程琦[1] 郑建铭[1] 黄翀[1] 陈明泉[1] 施光峰[1] 

机构地区：[1]复旦大学附属华山医院感染科,上海200040

出　　处：《中国医师杂志》2016年第3期328-332,共5页Journal of Chinese Physician

基　　金：国家自然科学基金资助项目（81101240,81371821）

摘　　要：目的 探讨慢加急性肝衰竭（AC LF）患者外周血树突状细胞的频率,表型和功能变化.方法 选择ACLF患者40例,慢性乙型肝炎（CHB）患者40例,20例健康者作对照（NC）组,流式细胞术检测髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC）频率.密度梯度法离心及免疫磁珠阳性选择法分离单核细胞,体外诱导培养为单核细胞衍生的树突状细胞（MoDC）,经刺激后,检测MoDC的表型,并通过混合淋巴细胞反应检测MoDC刺激同种异体T淋巴细胞增殖的能力.结果 ACLF组mDC频率较CHB组及NC组均明显降低（P＜0.01）,但CHB组与NC组差异无统计学意义（P =0.927）.与NC组相比,ACLF组和CHB组pDC的百分率均显著降低（P＜0.01）,但ACLF组和CHB组之间差异无统计学意义（P=0.112）.经poly（I∶C）刺激后,CHB组MoDC表面MHCⅡ类分子HLA-DR、成熟的标志CD83及协同刺激分子CD86和CD80平均荧光强度的表达均低于NC组,但高于ACLF组.HBV感染者MoDC刺激T细胞增殖的能力低于NC组,ACLF组降低尤为显著（P＜0.01）.结论 ACLF患者外周血mDC和pDC频率显著下降,MoDC表型缺失、成熟障碍以及功能低下,可能为慢加急性肝衰竭的发病机制之一.Objective To investigate the frequencies of circulating dendritic cell （DC） subsets and the function of monocyte-derived dendritic cells in patients with hepatitis B-related acute-on-chronic liver failure.Methods Peripheral blood was collected from hepatitis B-related acute-on-chronic liver failure patients （ACLF,n =40） and chronic hepatitis B （CHB,n =40） as well as normal controls （NCs,n =20）.Circulating myeloid dendritic cell （Mdc） and plasmic dendritic cell （pDC） frequencies in peripheral blood mononuclear cells （PBMC） were analyzed by flow cytometric analysis.Purified monocytes were isolated by combination of Histopaque-1.077 and CD14 Microbeads.Monocyte-derived dendritic cells （MoDCs） generated in vitro in the presence of interleukin （IL）-4 and granulocyte macrophage colony-stimulating factor upon activation by poly I：C.Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction （AMLR） of MoDCs were detected in patients with hepatitis B-related ACLF.Results The number of circulating mDC decreased only in patients with hepatitis B-related ACLF compared with that in normal controls.However,pDC numbers decreased in both CHB and ACLF patients.We observed a further decrease the pDC numbers in ACLF compared to CHB patients without statistical significance （P 〉 0.05）.MoDC from ACLF patients showed lower expression of costimulatory molecules CD80,CD86 and the mature marker CD83,as well as MHC Ⅱ molecule （HLA-DR） compared to CHB and NC group.Interestingly,MoDC impaired allostimulatory mixed lymphocyte reaction from ACLF patients compared to those in CHB patients and NCs.Conclusions Patients with hepatitis B-related ACLF have a significantly lower expression of surface markers and impaired AMLR of MoDC,as well as decreased number of circulating mDC and pDC,which may be partially related to HBV disease progression in these patients.

关 键 词：肝功能衰竭 急性/代谢 树突细胞/代谢 

分 类 号：R575.3[医药卫生—消化系统]