首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination exert helper function and predict antibody responses
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Human circulating influenza-CD4+ ICOS1+IL-21+ T cells expand after vaccination exert helper function and predict antibody responses

机译:疫苗接种后人循环中的流感CD4 + ICOS1 + IL-21 + T细胞会扩增发挥辅助功能并预测抗体反应

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摘要

Protection against influenza is mediated by neutralizing antibodies, and their induction at high and sustained titers is key for successful vaccination. Optimal B cells activation requires delivery of help from CD4+ T lymphocytes. In lymph nodes and tonsils, T-follicular helper cells have been identified as the T cells subset specialized in helping B lymphocytes, with interleukin-21 (IL-21) and inducible costimulatory molecule (ICOS1) playing a central role for this function. We followed the expansion of antigen-specific IL-21+ CD4+ T cells upon influenza vaccination in adults. We show that, after an overnight in vitro stimulation, influenza-specific IL-21+ CD4+ T cells can be measured in human blood, accumulate in the CXCR5ICOS1+ population, and increase in frequency after vaccination. The expansion of influenza-specific ICOS1+IL-21+ CD4+ T cells associates with and predicts the rise of functionally active antibodies to avian H5N1. We also show that blood-derived CXCR5ICOS1+ CD4+ T cells exert helper function in vitro and support the differentiation of influenza specific B cells in an ICOS1- and IL-21–dependent manner. We propose that the expansion of antigen-specific ICOS1+IL-21+ CD4+ T cells in blood is an early marker of vaccine immunogenicity and an important immune parameter for the evaluation of novel vaccination strategies.
机译:中和抗体介导了针对流感的保护作用,在高滴度和持续滴度下诱导它们是成功接种疫苗的关键。最佳的B细胞活化需要CD4 + T淋巴细胞提供帮助。在淋巴结和扁桃体中,T卵泡辅助细胞已被鉴定为专门帮助B淋巴细胞的T细胞亚群,其中白介素21(IL-21)和诱导型共刺激分子(ICOS1)在此功能中起着核心作用。我们跟踪了成人流感疫苗接种后抗原特异性IL-21 + CD4 + T细胞的扩增。我们显示,经过一夜的体外刺激后,可以在人血中测量流感特异性IL-21 + CD4 + T细胞,并在CXCR5 中积累− ICOS1 + 种群,接种后频率增加。流感特异性ICOS1 + IL-21 + CD4 + T细胞的扩增与禽H5N1的功能活性抗体相关并预测其增加。我们还显示,血液来源的CXCR5 - ICOS1 + CD4 + T细胞在体外发挥辅助功能并支持流感特异性B细胞的分化以依赖ICOS1和IL-21的方式进行。我们认为血液中抗原特异性ICOS1 + IL-21 + CD4 + T细胞的扩增是疫苗免疫原性的早期标志,评估新型疫苗接种策略的重要免疫参数。

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