Normal functional capacity in circulating myeloid and plasmacytoid dendritic cells in patients with chronic hepatitis C

Initial reports analyzing dendritic cell (DC) function in patients with hepatitis C virus (HCV) infection have been controversial. Here, we enumerate and characterize the function of circulating myeloid and plasmacytoid DCs. The results show lower percentages of myeloid DCs (0.62 vs. 0.83; P = .05) and plasmacytoid DCs (0.11 vs. 0.34; P = .004) in patients with chronic HCV infection than in healthy, non-HCV-infected individuals. Despite the lower numbers of circulating myeloid DCs present, no phenotypic or functional defects were identified. The lower percentage of plasmacytoid DCs resulted in decreased absolute interferon (IFN)-alpha production; however, when analyzed on a per-cell basis, plasmacytoid DCs from HCV-infected patients generated levels of IFN-alpha equivalent to those generated by DCs from healthy, non-HCV-infected individuals. Contrary to data from previous models (which attributed HCV pathogenesis to defects in the DC compartment), our data reveal functional DC subsets in patients with chronic HCV infection. These results are encouraging for DC-based HCV immunotherapy trials.     

Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B

Dendritic cells (DC) play an important role in the induction of T-cell responses. We hypothesize that the hampered antiviral T-cell response in chronic hepatitis B patients is a result of impaired dendritic cell function. In this study, we compared the number, phenotype and functionality of two important blood precursor DC, myeloid DC (mDC) and plasmacytoid DC (pDC), of chronic hepatitis B patients with healthy volunteers. No differences in percentages of mDC and pDC in peripheral blood mononuclear cells were observed between chronic hepatitis B patients and healthy controls. The allostimulatory capacity of isolated and in vitro matured mDC, but not of pDC, was significantly decreased in patients compared to controls. Accordingly, a decreased percentage of mDC expressing CD80 and CD86 was observed after maturation, compared to controls. In addition, mDC of patients showed a reduced capacity to produce tumor necrosis factor alpha after a stimulus with synthetic double-stranded RNA and interferon gamma. Purified pDC from patients produced less interferon alpha, an important antiviral cytokine, in response to stimulation with Staphylococcus aureus Cowan strain I than pDC isolated from controls. In conclusion, mDC and pDC are functionally impaired in patients with chronic hepatitis B. This might be an important way by which hepatitis B virus evades an adequate immune response, leading to viral persistence and disease chronicity.     

CpG ODN2216刺激慢性乙型肝炎患者浆样树突状细胞表型和功能的变化

目的观察慢性乙型肝炎患者外周血浆样树突状细胞(pDCs)的特点,并探讨pDCs在乙型肝炎病毒(HBV)感染发病机制中的作用。方法收集20例慢性乙型肝炎患者和15名健康人外周抗凝血,应用流式细胞仪分析pDCs的频率；同时检测CpG ODN2216刺激后pDCs表型及分泌干扰素(IFN)α功能的变化；并分析HBV慢性感染患者外周血pDCs频率、数量和功能的变化及其与临床病情的关系。结果应用免疫磁珠分选技术可得到纯度大于95%的pDCs。经CpG ODN2216刺激后纯化的pDCs能高表达共刺激分子CD80、CD86、CD40和CD83,并分泌大量的IFNα。与健康人比较,HBV感染患者外周血中pDCs频率明显下降,分别为0．287%±0．142%和0．192%±0．110%；经CpG ODN2216刺激后,其表面共刺激分子CD80和CD40表达明显下降,产生IFNα的能力也显著降低,分别为(3142．9±1292．3) pg/ml和(972．6±705．5)pg/ml。相关性分析表明,患者pDCs产生的IFNα水平与丙氨酸氨基转移酶水平呈明显负相关,但与血清病毒载量无明显相关性。结论CpG ODN2216可以刺激pDCs成熟并分泌大量IFNα。慢性乙型肝炎患者外周血pDCs频率、表型和功能明显下降,这可能是HBV持续感染的重要致病机制。     

慢性乙型肝炎患者外周血树突状细胞HBV DNA载量与其功能的关系

目的:探讨乙型肝炎患者外周血DCs HBV DNA载量与DCs功能的关系.方法:采集20例慢性乙型肝炎患者和10例健康人的抗凝外周静脉血,分离外周血单个核细胞(PBMCs),IL-4和GM-CSF的作用下培养使DCs增殖、成熟,以流式细胞技术分别检测DCs表面HLA-DR、CD-1α、CD80及CD86的表达:ELISA检测DCs培养上清液IL-12的水平,实时荧光定量PCR法检测DCs HBV DNA的载量,同种异体混合淋巴细胞反应检测DCs刺激同种异体T细胞增殖能力.结果:慢性乙型肝炎患者外周血DCs内亦可检测至HBv DNA,患者DCs表面HLA-DR、CD-1α、CD80及CD86的表达水平、DCs分泌IL-12水平及DCs刺激同种异体T细胞增殖能力均显著低于健康对照组,其中DCs HBV DNA阳性组较DCs HBV DNA阴性组下降更为明显(39.17±6.02 VS 60.11±7.92,46.03±5.52 VS 58.77±4.12,20.95±6.32 VS 35.24±7.41,25.16±6.05 VS 45.30±8.01,19.67±7.32VS 30.74±8.39,0.32±0.08 VS 0.59±0.11,均P＜0.01或0.05);HLA-DR、CD-1α、CD80及CD86的表达、IL-12水平及DCs刺激同种异体T细胞增殖能力与DCs HBV DNA载量呈显著负相关(r=0.713,-0.713,-0.623,-0.702,-0.525,-0.841,均P＜0.001).结论:慢性乙型肝炎患者外周血DCs可被HBV DNA感染,患者DCs HBV DNA载量与DCs功能有密切关系,病毒栽量低者DCs功能好,病毒栽量高者DCs功能差.     

Reduced numbers of plasmacytoid dendritic cells in aged blood donors

Dendritic cells (DC) play essential functions in both innate and adaptive immune responses. Peripheral blood DCs are divided into two major subsets, named conventional DC (cDC) and plasmacytoid DC (pDC), which play specific functions in the immune response. The absolute numbers of DCs (and their subsets) in peripheral blood may suffer variations due to physiological or pathological reasons, and therefore the enumeration of DC subsets in blood samples may be of clinical interest. However, to date this enumeration has produced controversial rather than consistent results. Here, using a two-tube platform approach, peripheral blood DCs have been enumerated in samples from healthy blood donors aged 18-65 years old. The results obtained showed a significant age-related decrease in pDC numbers, whilst cDC numbers remained unaltered. The different protocols used to define and enumerate DC subsets from blood samples may account for the controversial results reported before, thus emphasizing the importance of a general consensus to enumerate DCs. Reduced pDC numbers may be related to the higher susceptibility to infection and deficient response to vaccination often observed in aged individuals.     

慢性乙型肝炎病毒感染者外周血浆样树突状细胞Toll样受体9的表达和分泌功能

目的 探讨外周血浆样树突状细胞(pDC)Toll样受体(TLR)9的表达水平、pDC数量和分泌IFN-α能力的变化以及与慢性HBV感染状态的关系.方法 流式细胞分析技术检测69例慢性HBV感染患者(包括HBV携带者14例,慢性乙型肝炎患者30例,乙型肝炎肝硬化患者25例)和21例健康对照组外周血pDC频率和TLR9表达水平;用CpG ODN 2216刺激外周血单个核细胞(PBMC),并与PBMC共培养24 h,检测上清液中pDC产生IFN-α的能力;分析pDC数量、分泌IFN-α功能变化及其临床意义.应用SPSS 13.0进行统计学分析.结果 与健康对照组(62.6±10.7)相比,HBV携带者、慢性乙型肝炎、乙型肝炎肝硬化患者pDC表达TLR9平均荧光强度均有不同程度下降(P＜0.05).与慢性乙型肝炎患者(54.3±16.9)比较,HBV携带者及乙型肝炎肝硬化患者pDC表达TLR9平均荧光强度分别为44.5±10.3和45.9±13.8,差异有统计学意义(P＜0.05).健康对照组外周血pDC细胞频率为(0.88±0.54)%,明显高于慢性乙型肝炎患者的(0.51±0.36)%和乙型肝炎肝硬化患者的(0.5±0.3)%(P＜0.05).慢性HBV感染患者外周血pDC频率与血清ALT水平呈明显负相关(r=-0.341,P＜0.05).HBV携带者、慢性乙型肝炎患者、乙型肝炎肝硬化患者PBMC中pDC分泌IFN-α的水平分别为(291.10±198.16)、(285.34±155.56)和(206.92±148.36)pg/mL,明显低于健康者的(600.23±344.91)pg/mL(P＜0.05).结论 慢性HBV感染患者外周血pDC TLR9表达低下,外周血pDC频率和分泌IFN-α的能力明显降低,这可能是HBV持续感染的重要机制.     

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

目的对慢性丙型肝炎患者Ⅰ型树突状细胞（dendritic cell 1,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、HBVDNA水平与DC1数量之间均存在负相关趋势;3例完成6个月仪一干扰素治疗的患者,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。     

Reduced numbers and impaired ability of myeloid and plasmacytoid dendritic cells to polarize T helper cells in chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection induces a wide range of chronic liver injuries. The mechanism by which HCV evades the immune surveillance system remains obscure. Blood dendritic cells (DCs) consist of myeloid and plasmacytoid subsets that play distinct roles in the regulation of antivirus immune responses; however, their roles in the pathogenesis of HCV infection are yet to be determined. We compared the numbers and functions of myeloid and plasmacytoid DCs between 43 patients with chronic hepatitis and 26 age-matched healthy volunteers. Absolute numbers of myeloid DCs, plasmacytoid DCs, and DC progenitors in the periphery were significantly lower in patients with chronic hepatitis than in healthy volunteers. Myeloid and plasmacytoid DCs from the patients had impaired abilities to stimulate allogeneic CD4 T cells and to produce interleukin (IL)-12 p70 and interferon- alpha , compared with those from healthy volunteers. After exposure to naive CD4 T cells, myeloid DCs from the patients were less able to drive the T helper type 1 response, whereas myeloid and plasmacytoid DCs from the patients primed more IL-10-producing cells than did those from healthy volunteers. In conclusion, in chronic HCV infection, both types of blood DCs are reduced and have an impaired ability to polarize T helper cells.     

复合干扰素α治疗对慢性乙型肝炎患者浆样树突状细胞及淋巴细胞亚群的影响

目的动态观察慢性乙型肝炎患者重组复合干扰素(CIFN)α治疗过程中PDC、淋巴细胞亚群的变化。方法采用流式细胞分析技术检测23例慢性乙型肝炎患者CIFN治疗过程中外周血浆样树突状细胞(PDC)和淋巴细胞亚群百分比及数量。结果经CIFN治疗后,患者的应答率为43.5%。外周血PDC的百分比和绝对数显著减少(P值均<0.05),有效组与无效组PDC百分比和绝对数平均值在同一时间点无明显差别。同时CD3(?)细胞、CD4(?) T淋巴细胞、B淋巴细胞明显减少(P值均<0.05),CD4/CD8明显下降(P<0.05),但在治疗的24周及随访24周后患者CD8(?)T淋巴细胞、自然杀伤细胞有增加(P<0.05)。结论经CIFN治疗,慢性乙型肝炎患者外周血PDC、CD8(?)T淋巴细胞、自然杀伤细胞数量出现变化,部分患者可以获得持续性病毒学及生化学应答。     

慢性丙型肝炎患者树突状细胞功能的研究

目的　探讨树突状细胞 (DC)与慢性丙型肝炎患者体内病毒持续感染的关系。方法　从外周血分离单核细胞 ,用含粒细胞、巨噬细胞集落刺激因子 (GM CSF) ,白细胞介素 (IL) 4的AIM V无血清培养基诱导培养DC。观察DC外部形态和超微结构 ,检测DC表型 ,进行混合淋巴细胞反应(MLR) ,检测DC诱导同种异体静止T细胞增殖的能力和上清中细胞因子水平。结果　实验组DCCD86表达率为 (5 2 4± 13 3) % ,明显低于对照组的 (83 7± 15 8) % (P <0 0 1) ;实验组DC诱导同种异体静止T细胞增殖的能力每分钟液闪计数值 (cpm)为 192 4 5± 2 788,明显低于对照组的 2 6 5 2 9± 32 18(P <0 0 1) ;实验组MLR中IL 12p40 平均值为 (40 4± 10 3)ng/L ,干扰素γ平均值为 (7891± 82 1)ng/L ,分别低于对照组 (80 2± 2 0 5 )ng/L和 (13490± 15 5 4 )ng/L(P <0 0 0 5 )。结论　慢性丙型肝炎患者DC功能低下 ,提示与HCV持续感染有关。     

慢性乙型肝炎患者单核细胞来源树突状细胞Toll样受体的表达特征分析

目的观察慢性乙型肝炎（CHB）患者单核细胞来源树突状细胞（moDC）Toll样受体（TLR）的表达，并分析抗病毒相关TLR（TLR3、TLR4、TLR7、TLR8、TLR9）在CHB患者moDC的表达特征及意义。方法用羟乙基淀粉（HES）分离10例CHB患者及15例健康对照外周血单个核细胞（PBMC），经重组人粒细胞-巨噬细胞集落刺激因子（rhGM-CSF）、重组人白细胞介素4（rhIL-4）诱导培养树突状细胞（DC），经流式细胞仪用特异性单克隆抗体检测不同成熟阶段DC的TLR表达，并以HBcAg负载未成熟DC，应用FACS分析HBcAg的负载效率及细胞内IFN-γ、IL-4表达水平。结果moDC不同成熟阶段TLR的表达水平不同；CHB患者的未成熟moDC（imDC）表达的TLR7、TLR8低于健康对照（75．9％、1．0％比98．4％、15．4％，P〈0．05），CHB患者成熟moDC（mDC）表达TLR3、TLR7低于健康对照（9．5％、79．7％比11．5％、90．7％，P〈0．05）；应用HBcAg分别于细胞培养第3天和第5天冲击DC，第1次冲击后48hHBcAg的膜内、膜外负载率分别为53．0％和7．5％，第2次冲击后分别为80．2％和19．0％；HBcAg负载或未负载的moDC，均刺激淋巴细胞高表达IFN-γ，较少表达或不表达IL-4，呈现显著的Th1免疫应答。结论CHB患者moDC的抗病毒相关TLR表达低下，且可能是其DC功能低下的重要原因之一；应用HBcAg冲击imDC，可使其有效负载HBcAg，负载后DC的成熟过程及功能不受影响，仍以诱导Th1免疫应答反应为主。     

Circulating plasmacytoid dendritic cells in acutely infected patients with hepatitis C virus genotype 4 are normal in number and phenotype

The incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection.     

Cell culture-produced hepatitis C virus impairs plasmacytoid dendritic cell function

Previous studies suggested a functional impairment of dendritic cells (DCs) in patients with chronic hepatitis C. To investigate whether this effect was mediated by a direct interaction of hepatitis C virus (HCV) with DCs, we studied the effects of infectious cell culture-produced hepatitis C virus (HCVcc) on peripheral blood mononuclear cells (PBMCs), ex vivo isolated plasmacytoid, and myeloid DCs and in vitro generated monocyte-derived DCs of healthy blood donors. HCVcc inhibited toll-like receptor (TLR)-9 (CpG and herpes simples virus)-mediated interferon alpha (IFN-alpha) production by peripheral blood mononuclear cells (PBMC) and plasmacytoid DCs. This inhibitory effect was also observed in response to ultraviolet (UV)-inactivated, noninfectious HCVcc, and it was not abrogated by neutralizing antibodies, and thus did not appear to require DC infection. Influenza A virus restored maturation and TLR9-mediated IFN-alpha production. In contrast to its effect on plasmacytoid DCs, HCVcc did not inhibit TLR3-mediated and TLR4-mediated maturation and interleukin (IL)-12, IL-6, IL-10, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) production by myeloid DCs and monocyte-derived DCs. Likewise, HCVcc did neither alter the capacity of myeloid DCs nor monocyte-derived DCs to induce CD4 T cell proliferation. Whereas phagocytosis of apoptotic hepatoma cells resulted in DC maturation, this effect was independent of whether the phagocytosed Huh7.5.1 cells were infected with HCVcc. In contrast to HCVcc, vaccinia virus inhibited maturation and TNF-alpha expression of myeloid DC as well as maturation and IL-6 and IL-10 production of monocyte-derived DC. CONCLUSION: HCVcc inhibited plasmacytoid DCs but not myeloid-derived and monocytoid-derived DCs via a direct interaction that did not require infection. The response of plasmacytoid DCs to influenza A virus infection was not impaired.     

长效干扰素α-2a治疗慢性乙型肝炎过程中外周血浆样树突状细胞的变化及其与疗效的关系

目的 观察长效干扰素(PEG-IFN α-2a)治疗慢性乙型肝炎过程中外周血浆样树突状细胞(pDC)亚群的变化及其与临床疗效的关系. 方法 41例慢性乙型肝炎患者接受PEG-IFN α-2a(180 μg)每周皮下注射一次,治疗48周;治疗过程中检测肝功能、血清HBV病毒学标志物和HBVDNA,在治疗前及治疗开始后2、12、24、36、48周分别检测外周血pDC数量和功能及Toll样受体(TLR)9的表达水平、血清肿瘤坏死因子(TNF)α及IFN γ水平.对数据进行成组设计t检验、非参数检验、重复测量资料的方差分析. 结果 应答组与无应答组比较,TLR9平均荧光强度、pDC数量及INF α分泌能力在治疗2周时均明显下降,应答组在12周时TLR9平均荧光强度恢复(66.25±13.10),无应答组仍处于低水平(51.47±16.85),差异有统计学意义(t=2.478,P＜0.05);12周时应答组pDC数量恢复(5.24±1.61),无应答组为(3.74±1.25),差异有统计学意义(t=2.644,P＜0.05);12周时应答组IFN α分泌能力明显升高(459.94±200.27) pg/ml,显著高于无应答组[(237.18± 123.57)pg/ml],差异有统计学意义(t=2.942,P＜0.05).治疗24周时,应答组血清IFN γ水平明显升高[(67.81±16.64) pg/ml],显著高于无应答组[(43.73± 15.97) pg/ml],差异有统计学意义(t=3.396,P＜ 0.05);TNFα水平为[(268.94±64.32)pg/ml],也显著高于无应答组[(206.45±78.28) pg/ml],差异有统计学意义(t=2.22,P＜0.05).结论 pDC在PEG-IFNα-2a治疗诱发的早期免疫应答中发挥重要作用,抗病毒治疗过程中pDC数量和功能的恢复可能是机体抗病毒治疗应答的重要因素.     

Plasmacytoid dendritic cells in acute and chronic hepatitis C virus infection

Chronic evolution of acute hepatitis C (aHC) occurs in more than 80% of patients but can frequently be prevented by early treatment with interferon (IFN)-alpha. Plasmacytoid dendritic cells (pDCs) are the major endogenous IFN-alpha producers, but their role in aHC is unknown. In this study, frequency, phenotype, and pDC function were analyzed in 13 patients with aHC and 32 patients with chronic hepatitis C (cHC) compared with 20 healthy controls, 33 sustained responders to antiviral treatment, 14 patients with acute hepatitis B (aHB), and 21 patients with nonviral inflammatory disease. In aHC, pDCs in the peripheral blood were significantly reduced compared with healthy controls (median, 0.1% vs. 0.36%, P < .0005) and were inversely correlated to alanine aminotransferase levels (r = -0.823; P < .005). Circulating pDCs in aHC were immature, as determined via reduced expression of HLA-DR and CCR7, and produced little amounts of IFN-alpha (median, 3.5 pg/50,000 peripheral blood mononuclear cells [PBMCs] vs. 498.4 pg/50,000 PBMCs in healthy controls; P < .0005). Less pronounced changes were present in cHC (median, 0.17%, 28.0 pg/50,000 PBMCs IFN-alpha, respectively). However, a significantly reduced frequency and IFN-alpha production was also found in self-limited aHB (median 0.1%, 8.6 pg/50,000 PBMCs) and in patients with nonviral inflammatory disease (median 0.19%, 7.5 pg/50,000 PBMCs). In conclusion, in aHC frequency and IFN-alpha-producing capacity of peripheral blood pDCs are dramatically reduced and inversely correlated with the degree of liver inflammation. In cHC there is incomplete recovery of pDC function, which, however, could be solely due to the chronic inflammatory state.     

肝素对慢性乙型肝炎患者树突状细胞免疫功能的作用

慢性乙型肝炎(CHB)发生的重要原因之一是患者的机体不能对乙型肝炎病毒川BV)形成充分有效的免疫应答以清除病毒。树突状细胞(DC)是目前发现的功能最强的抗原呈递细胞,在激活T细胞介导的免疫中具有重要的作用。近期文献报道及我们的研究结果提示CHB患者DC不仅数量较少而且发育障碍、功能低下。所以促进CHB患者DC发育并改善其功能,对提高CHB患者的免疫功能以清除体内的HBV有重要意义。本文通过研究肝素在体外对CHB患者DC功能的调节作用,为寻找能促进DC成熟的经济有效的诱导因子提供实验依据。一、材料与方法 1．材料：巨噬细胞集落刺激因子(GM-CSF)(北京医科大学免疫室提供)；白细胞介素(IL)4、肿瘤坏死因子(TNF) α、干扰素(IFN)γ(美国Promega公司产品)；荧光标记的抗人CDla、CD40、CD80、CD83、CD86、人类白细胞抗原-DR 单克隆抗体(美国lmmunotech公司产品)；RPMI 1640培养基、MTT、异硫氰酸荧光素(FITC)-Dextran(美国Sigma     

CpG-ODN联合HBsAg对慢性乙型肝炎患者外周血树突状细胞表型和功能的影响

目的　研究含非甲基化CpG基序的免疫刺激寡核苷酸 (CpG- ODN)与重组HBsAg对慢性乙型肝炎患者 (CHB)外周血树突状细胞 (dendriticcell ,DC)表型和功能的影响。方法　以重组人GM CSF、IL 4自CHB患者和健康者外周血单个核细胞诱导扩增DC ;以CpG ODN和HBsAg单独或联合刺激DC ,并与TNF α比较 ,评价其对DC表达表面分子HLA DR、CD86、CD1a ,分泌IL 12p70以及刺激同种T细胞增殖能力的影响 ;同时检测血浆TGF- β、IFN- γ含量。 结果　与PBS组比 ,CpG- ODN单用或联合HBsAg均能明显提高CHB患者DC表面分子HLA DR的表达 ,使IL- 12分泌增加 ,刺激同种T细胞增殖的能力亦增强 ,CpG ODN联合HBsAg尚能明显提高CD1a的表达 ;CpG- ODN的上述刺激作用类似于TNF α ;CHB患者血浆TGF- β、IFN -γ含量明显高于正常对照。 结论　CpG -ODN与TNF α一样能够促进CHB患者外周血DC分化和成熟 ;CpG- ODN与HBsAg联合刺激能协同增强DC的特异性抗原递呈作用 ;CHB患者的细胞因子环境可能是DC功能沉默的重要原因。