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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Complementarity-determining region 3 size spectratypes of T cell receptor beta chains in CD8+ T cells following antiviral treatment of chronic hepatitis B.
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Complementarity-determining region 3 size spectratypes of T cell receptor beta chains in CD8+ T cells following antiviral treatment of chronic hepatitis B.

机译:抗病毒治疗慢性乙型肝炎后,CD8 + T细胞中T细胞受体β链的互补决定区3尺寸光谱类型。

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An increased CD8(+) T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8(+) T cells at these time points predict the virological response to therapy. Peripheral blood CD8(+) T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) beta chain variable region (Vbeta) gene family was analyzed, and the changes in the numbers of Vbeta families with clonal expansions were compared in subjects with (n = 12) and without (n = 8) a virological response (52 week HBV DNA < 300 copies/ml). The number of CD8(+) TCR Vbeta families with clonal expansions at 12 weeks relative to baseline (median [10th to 90th percentile], +2.5 [0 to +7] versus +1 [0 to +2], P = 0.03) and at 24 weeks relative to 12 weeks (+1 [0 to +2] versus -1 [-3 to +4], P = 0.006) was higher in subjects with a virological response versus subjects without a virological response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P < 0.0001) in responders. Increased numbers of CD8(+) T cell expansions after antiviral therapy are associated with a virological response to treatment. These CD8(+) T cells are a potential target for a therapeutic vaccine for chronic hepatitis B.
机译:在开始对慢性乙型肝炎进行抗病毒治疗后的12至24周内,对乙型肝炎病毒(HBV)肽的CD8(+)T细胞应答增加。尚不清楚这些细胞是否具有抗病毒功能。这项研究的目的是确定在这些时间点CD8(+)T细胞的克隆扩增是否可以预测对治疗的病毒学应答。在基线,12周和24周时,从20例接受拉米夫定或替比夫定治疗的慢性乙型肝炎患者中获得外周血CD8(+)T细胞。分析了每个T细胞受体(TCR)β链可变区(Vbeta)基因家族的CDR3光谱类型,并比较了有(n = 12)和没有(n = 12)的受试者中具有克隆扩增的Vbeta家族数目的变化。 8)病毒学应答(52周HBV DNA <300拷贝/ ml)。相对于基线在12周时具有克隆扩增的CD8(+)TCR Vbeta家族数量(中位[第10至90个百分位数],+ 2.5 [0至+7]对+1 [0至+2],P = 0.03)相较于没有病毒学应答的受试者,有病毒应答的受试者相对于没有病毒应答的受试者,在24周相对于12周(+1 [0至+2]与-1 [-3至+ 4,P = 0.006])更高-2(IL-2),但外周血单核细胞中的IL-21 mRNA水平没有。应答者在12周时新扩张的持续时间更长(P <0.0001)。抗病毒治疗后CD8(+)T细胞扩增数量的增加与治疗的病毒学应答有关。这些CD8(+)T细胞是慢性乙型肝炎治疗疫苗的潜在靶标。

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