Carotenuto Patrizia, Artsen Andrè, Niesters Hubert G, Osterhaus Albert D, Pontesilli Oscar
Department of Virology, ErasmusMC, Dr. Molewaterplein 50, 3015GE Rotterdam, The Netherlands.
J Med Virol. 2009 Feb;81(2):332-9. doi: 10.1002/jmv.21333.
T lymphocyte responses to hepatitis B virus (HBV) core antigen (HBcAg) are vigorous and easily detectable in vitro during recovery from acute hepatitis B but significantly weaker in patients with chronic HBV infection. In contrast, T cell responses to hepatitis B surface antigen (HBsAg) are almost undetectable during infection and even in a substantial fraction of subjects receiving vaccination with HBsAg. The aim of this study was to investigate whether the use of dendritic cells (DCs) in an in vitro assay could increase the detection of HBV-specific T cells in these conditions. Autologous monocyte-derived DCs, compared to direct HBsAg addition to the cultures, increased the stimulation of HBs- specific T cells. These were detected in 73% of healthy subjects who had recently received hepatitis B vaccine and in 43% of patients recovering from acute hepatitis B. Likewise, proliferation in response to DC-presented HBcAg was detected in both CD4(+) and CD8(+) T cells from the majority of chronic hepatitis B patients. A longitudinal evaluation of HBc-specific T cell responses during and after a 1-year treatment with pegylated interferon (IFN)-alpha showed that HBc-specific CD4(+) T cell responses had no correlation with sustained virus suppression whereas CD8(+) T cell responses were more frequently detected in patients able to control HBV replication after therapy interruption. The use of autologous DCs as antigen-presenting cells appears applicable to clinically relevant in vitro evaluation of T cell responses, particularly in those conditions characterized by low frequency of circulating antigen-specific cells and suboptimal in vivo activation.
在急性乙型肝炎恢复期，T淋巴细胞对乙型肝炎病毒（HBV）核心抗原（HBcAg）的反应强烈且在体外易于检测，但在慢性HBV感染患者中则明显较弱。相比之下，在感染期间甚至在相当一部分接受HBsAg疫苗接种的受试者中，T细胞对乙型肝炎表面抗原（HBsAg）的反应几乎检测不到。本研究的目的是调查在体外试验中使用树突状细胞（DC）是否能增加在这些情况下HBV特异性T细胞的检测。与直接向培养物中添加HBsAg相比，自体单核细胞衍生的DC增强了HBs特异性T细胞的刺激。在最近接种乙肝疫苗的73%的健康受试者和43%的急性乙型肝炎恢复期患者中检测到了这些细胞。同样，在大多数慢性乙型肝炎患者的CD4(+)和CD8(+) T细胞中都检测到了对DC呈递的HBcAg的增殖反应。对聚乙二醇化干扰素（IFN）-α治疗1年期间及之后的HBc特异性T细胞反应进行纵向评估发现，HBc特异性CD4(+) T细胞反应与持续病毒抑制无关，而在治疗中断后能够控制HBV复制的患者中更频繁地检测到CD8(+) T细胞反应。使用自体DC作为抗原呈递细胞似乎适用于T细胞反应的临床相关体外评估，特别是在那些以循环抗原特异性细胞频率低和体内激活不理想为特征的情况下。
