Protective neutralizing influenza antibody response in the absence of T follicular helper cells

Protective neutralizing influenza antibody response in the absence of T follicular helper cells
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DOI:
10.1038/ni.3563
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发表时间:
2016-12-01
期刊:
影响因子:
30.5
通讯作者:
Kubo, Masato
Kubo, Masato
中科院分区:
医学1区
文献类型:
--
作者:
Miyauchi, Kosuke;Sugimoto-Ishige, Akiko;Kubo, Masato

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病毒感染诱导T滤泡辅助(T- fh)和T辅助1 (T(H)1)细胞的发育。尽管T- fh细胞在抗病毒体液免疫中很重要,但T(H)1细胞对保护性抗体反应的贡献尚不清楚。我们发现IgG2抗体在灭活甲型流感病毒(IAV)疫苗接种反应中占主导地位,并负责对致病性H5N1和大流行性H1N1 IAV毒株的致命攻击产生保护性免疫,即使在缺乏T-FH细胞和生发中心的小鼠中也是如此。由T(H)1细胞分泌的细胞因子白介素-21和干扰素- γ是观察到的更持久和更高滴度的IgG2保护性抗体所必需的。我们的研究结果表明,T(H)1诱导可能是一种有前途的策略,可以产生有效的中和抗体来对抗新出现的流感病毒。
Virus infection induces the development of T follicular helper (T-FH) and T helper 1 (T(H)1) cells. Although T-FH cells are important in anti-viral humoral immunity, the contribution of T(H)1 cells to a protective antibody response remains unknown. We found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked T-FH cells and germinal centers. The cytokines interleukin-21 and interferon-gamma, which are secreted from T(H)1 cells, were essential for the observed greater persistence and higher titers of IgG2 protective antibodies. Our results suggest that T(H)1 induction could be a promising strategy for producing effective neutralizing antibodies against emerging influenza viruses.