T Cell-Mediated Protection against Lethal 2009 Pandemic H1N1 Influenza Virus Infection in a Mouse Model
T Cell-Mediated Protection against Lethal 2009 Pandemic H1N1 Influenza Virus Infection in a Mouse Model
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DOI：
10.1128/jvi.01812-10
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Topham, David J.
中科院分区：
文献类型：
--
作者：
Guo, Hailong;Santiago, Felix;Topham, David J.
流感病毒基因片段，特别是血凝素（HA）和神经氨酸酶（NA）基因片段的基因突变和重组，导致抗原漂移和转移，是流感病毒逃避原有免疫的主要策略。这种现象的最新例子是2009年开始的21世纪世纪第一次H1N1流感大流行。针对1930年前流行的H1N1病毒产生的交叉反应抗体显示出对2009年大流行病毒的保护活性。交叉反应性T细胞应答也可以有助于保护，但缺乏对这种观点的体内支持。为了探索体内保护机制，我们用H1和H3流感病毒分离株致敏小鼠，并用来自2009年H1N1 A/CA/04/09病毒的病毒（命名为CA/E3/09）再次攻击它们。我们发现用H1和H3同型和异型亚型流感病毒引发可保护免受致命的CA/E3/09病毒攻击。这些致敏小鼠的恢复期血清在体外没有中和活性，在体内也没有保护作用。然而，T细胞耗竭研究表明，CD 4和CD 8 T细胞都有助于保护。总之，这些结果表明，在用远端相关病毒初始引发后建立的交叉反应性T细胞可以是预防疾病和控制大流行性H1N1流感病毒感染的重要组成部分。我们的研究结果强调了建立交叉反应性T细胞应答对预防现有或新出现的大流行性流感病毒的重要性。
Genetic mutation and reassortment of influenza virus gene segments, in particular those of hemagglutinin (HA) and neuraminidase (NA), that lead to antigenic drift and shift are the major strategies for influenza virus to escape preexisting immunity. The most recent example of such phenomena is the first pandemic of H1N1 influenza of the 21st century, which started in 2009. Cross-reactive antibodies raised against H1N1 viruses circulating before 1930 show protective activity against the 2009 pandemic virus. Cross-reactive T-cell responses can also contribute to protection, but in vivo support of this view is lacking. To explore the protection mechanisms in vivo, we primed mice with H1 and H3 influenza virus isolates and rechallenged them with a virus derived from the 2009 H1N1 A/CA/04/09 virus, named CA/E3/09. We found that priming with influenza viruses of both H1 and H3 homo- and heterosubtypes protected against lethal CA/E3/09 virus challenge. Convalescent-phase sera from these primed mice conferred no neutralization activity in vitro and no protection in vivo. However, T-cell depletion studies suggested that both CD4 and CD8 T cells contributed to the protection. Taken together, these results indicate that cross-reactive T cells established after initial priming with distally related viruses can be a vital component for prevention of disease and control of pandemic H1N1 influenza virus infection. Our results highlight the importance of establishing cross-reactive T-cell responses for protecting against existing or newly emerging pandemic influenza viruses.