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首页> 外文期刊>Thrombosis and Haemostasis: Journal of the International Society on Thrombosis and Haemostasis >Replacement therapy with plasma-derived factor VIII concentrates induces skew in T-cell receptor usage and clonal expansion of CD8+ T-cell in HIV-seronegative hemophilia patients.
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Replacement therapy with plasma-derived factor VIII concentrates induces skew in T-cell receptor usage and clonal expansion of CD8+ T-cell in HIV-seronegative hemophilia patients.

机译：HIV血清阴性血友病患者血浆衍生的VIII因子浓缩物替代疗法可引起T细胞受体使用偏向和CD8 + T细胞的克隆扩增。

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摘要

Replacement therapy with factor VIII (FVIII) products causes immune abnormalities in human immunodeficiency virus (HIV)-seronegative hemophilia patients. However, the question remains why an absolute increase in the number of CD8+ T-cells and diminished proliferation responses of lymphocytes to antigen stimulation in vitro occurs in HIV-seronegative hemophilia patients. To examine whether the FVIII products induce skewing of T-cell receptor (TCR) repertoires, TCR variable region alpha-chain and beta-chain repertoires were analyzed for peripheral blood mononuclear cells (PBMCs) from 15 hemophilia patients treated with heated and/or non-heated plasma-derived FVIII concentrates and 10 age-matched healthy adults. Also, T-cell clonality was compared between these groups using complementarity-determining region 3 (CDR3) size spectratyping. The skewing of TCR repertoires was significantly greater for hemophilia patients than healthy controls. The extent of T-cell clonality was greater for hemophilia patients than the controls, indicating that clonal T-cells frequently expanded in hemophilia patients. The skew in TCR usage and clonal expansion were primarily observed in patients treated with non-heated plasma-derived products. The spectratyping and sequencing of CDR3 regions revealed that the clonal expansion of T-cells was observed for CD8+ T-cells, but not CD4+ T-cells. These results suggest that extensive expansion of CD8+ T-cells is induced by some viruses other than HIV present in FVIII preparations, and the resulting accumulation of CD8+ T-cells is responsible for changes in peripheral T-cell population in HIV-seronegative hemophilia patients.
机译：用VIII因子（FVIII）产品替代疗法会导致人类免疫缺陷病毒（HIV）血清阴性血友病患者出现免疫异常。但是，问题仍然存在，为什么在HIV血清阴性血友病患者中会出现CD8 + T细胞数量的绝对增加和淋巴细胞对抗原刺激的淋巴细胞增殖反应的减弱。为了检查FVIII产物是否诱导T细胞受体（TCR）库的倾斜，分析了15例接受加热和/或非加热治疗的血友病患者的TCR可变区α链和β链库中的外周血单核细胞（PBMC）。加热血浆衍生的FVIII浓缩液和10位年龄匹配的健康成年人。同样，使用互补决定区3（CDR3）大小谱型比较了这些组之间的T细胞克隆性。血友病患者的TCR库的偏倚明显大于健康对照。血友病患者的T细胞克隆程度比对照组大，这表明血友病患者的克隆性T细胞经常扩增。主要在非加热血浆衍生产品治疗的患者中观察到TCR使用率和克隆扩增的偏斜。 CDR3区的光谱分型和测序表明，对于CD8 + T细胞，而非CD4 + T细胞，观察到T细胞的克隆扩增。这些结果表明，CDVIII + T细胞的广泛扩增是由FVIII制剂中存在的HIV以外的其他病毒引起的，并且CD8 + T细胞的积累导致HIV血清阴性血友病患者外周T细胞群体发生变化。

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