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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >The relationship between human effector and memory T cells measured by ex vivo and cultured ELISPOT following recent and distal priming.
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The relationship between human effector and memory T cells measured by ex vivo and cultured ELISPOT following recent and distal priming.

机译:在最近和远端启动后,通过离体和培养的ELISPOT测量的人类效应子与记忆T细胞之间的关系。

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Maintenance of T-cell responses is an essential feature in protection from many infectious diseases that must be harnessed in vaccination. The relationship between effector T-cell responses and more durable and highly proliferative T-cell memory, particularly in humans, is not well understood. In this study, effector T-cell responses were measured by overnight ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell assay (ELISPOT), whereas memory T cells were measured by 10-day culture followed by IFN-gamma ELISPOT (cultured ELISPOT). We observed a significant correlation between IFN-gamma responses to CD4-stimulatory, but not to CD8-stimulatory, recall antigens measured by these assays, suggesting a divergence in regulation. In vaccine trial participants who received a prime-boost vaccination regimen comprising malaria antigens delivered by poxviruses, there was a correlation between ex vivo and cultured responses on day 7, but not 3 months post-vaccination, with the ratio of cultured : ex vivo response increasing over time. To compare responses revealed by cultured ELISPOT in more detail, tetramers comprising viral recall antigens were used to ascribe effector-memory and central-memory T-cell phenotypes through CCR7 and CD62L costaining. For CD8(+) responses the effector phenotype decreased during the initial culture period and memory populations remained high within the resulting 20-fold to 50-fold increased IFN-gamma-secreting or tetramer(+) population. This was less marked for CD4(+) responses, which had higher starting memory phenotype. Depletion of these central-memory T-cell populations generally ablated responses in cultured ELISPOT and reduced ex vivo responses. This study highlights differences between CD4(+) and CD8(+) effector and memory T cells, and the more complex phenotype of CD4(+) T cells.
机译:维持T细胞反应是预防许多传染病必须接种的重要特征。效应T细胞应答与更持久和高度增殖的T细胞记忆之间的关系,尤其是在人类中,尚未得到很好的理解。在这项研究中,通过过夜的离体干扰素-γ(IFN-γ)酶联免疫吸附点形成细胞试验(ELISPOT)测定了效应T细胞反应,而记忆T细胞则是通过10天培养,然后进行IFN测定-gamma ELISPOT(培养的ELISPOT)。我们观察到,IFN-γ对CD4刺激但对CD8刺激的召回抗原的反应之间存在显着相关性,这些抗原通过这些检测方法测定,表明调节存在差异。在接受包含痘病毒提供的疟疾抗原的初免-加强疫苗接种方案的疫苗试验参与者中,在接种后第7天(而非疫苗接种后3个月),离体培养反应与培养应答之间存在相关性,与培养物:离体应答的比率有关随着时间增加。为了更详细地比较培养的ELISPOT所揭示的应答,包含病毒召回抗原的四聚体被用于通过CCR7和CD62L共鉴定归因于效应记忆和中央记忆T细胞表型。对于CD8(+)反应,效应子表型在初始培养期间降低,并且记忆种群在导致IFN-γ分泌增加或四聚体(+)种群增加20到50倍的范围内仍然很高。 CD4(+)反应,这具有较高的起始记忆表型较少标记。这些中央记忆T细胞群体的耗竭通常消除了培养的ELISPOT中的应答并降低了离体应答。这项研究强调了CD4(+)和CD8(+)效应子与记忆T细胞之间的差异,以及CD4(+)T细胞的更复杂的表型。

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