Heterosubtypic immunity to influenza A virus in mice lacking IgA, all Ig, NKT cells, or γδ T cells
Heterosubtypic immunity to influenza A virus in mice lacking IgA, all Ig, NKT cells, or γδ T cells
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DOI：
10.4049/jimmunol.166.12.7437
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发表时间：
2001-06-15
影响因子：
4.4
通讯作者：
Epstein, SL
中科院分区：
文献类型：
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作者：
Benton, KA;Misplon, JA;Epstein, SL
对不同亚型流感病毒的广泛交叉保护机制（称为异亚型免疫）仍不完全清楚。我们使用敲除小鼠品系来检测缺乏IgA、所有Ig和B细胞、NKT细胞（CD1敲除小鼠）或γ δ T细胞的异亚型免疫的潜力。用甲型流感病毒活体免疫小鼠，并与不相关的乙型流感病毒免疫对照组进行比较。IgA（-/-）小鼠在对对照组致命的异亚型病毒的全呼吸道攻击中存活下来。IgA（-/-）小鼠在受到限于上呼吸道的异亚型攻击后，也能清除鼻咽和肺部的病毒，在上呼吸道，IgA已被证明发挥重要作用。Ig（-/-）小鼠控制了异亚型攻击病毒在肺中的复制。CD4（+）或CD8(+) T细胞亚群的急性耗竭消除了这种病毒的清除，从而表明在缺乏Ig的情况下，CD4（+）和CD8(+) T细胞都需要保护。Ig（-/-）小鼠的这些结果表明，CD4(+) T细胞可以通过其他机制发挥作用，而不是帮助B细胞产生抗体。与野生型小鼠一样，CD1（-/-）小鼠和γ δ(-/-)小鼠在致死性异亚型挑战中存活下来。在γ δ(-/-)小鼠中，CD4（+）和CD8（+）细胞的急性耗竭消除了异亚型保护，但在B6对照组中没有，这表明γ δ T细胞有贡献。我们的研究结果表明，在这些基因敲除小鼠中缺乏的Ab和细胞亚群并不是异亚型保护所必需的，但每一个都可能在多方面的反应中发挥作用，作为一个整体比其任何部分都更有效。
The mechanisms of broad cross-protection to influenza viruses of different subtypes, termed heterosubtypic immunity, remain incompletely understood. We used knockout mouse strains to examine the potential for heterosubtypic immunity in mice lacking IgA, all Ig and B cells, NKT cells (CD1 knockout mice), or gamma delta T cells. Mice were immunized with live influenza A virus and compared with controls immunized with unrelated influenza B virus. IgA(-/-) mice survived full respiratory tract challenge with heterosubtypic virus that was lethal to controls. IgA(-/-) mice also cleared virus from the nasopharynx and lungs following heterosubtypic challenge limited to the upper respiratory tract, where IgA has been shown to play an important role. Ig(-/-) mice controlled the replication of heterosubtypic challenge virus in the lungs. Acute depletion of CD4(+) or CD8(+) T cell subsets abrogated this clearance of virus, thus indicating that both CD4(+) and CD8(+) T cells are required for protection in the absence of Ig. These results in Ig(-/-) mice indicate that CD4(+) T cells can function by mechanisms other than providing help to B cells for the generation of Abs. Like wild-type mice, CD1(-/-) mice and gamma delta (-/-) mice survived lethal heterosubtypic challenge. Acute depletion of CD4(+) and CD8(+) cells abrogated heterosubtypic protection in gamma delta (-/-) mice, but not B6 controls, suggesting a contribution of gamma delta T cells. Our results demonstrate that the Ab and cellular subsets deficient in these knockout mice are not required for heterosubtypic protection, but each may play a role in a multifaceted response that as a whole is more effective than any of its parts.