Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice.
Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice.
复制标题
在B淋巴细胞缺陷小鼠中对致命流感病毒感染的抗性和恢复。
DOI：
10.1084/jem.186.12.2063
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发表时间：
1997-12-15
影响因子：
15.3
通讯作者：
Braciale, T J
中科院分区：
文献类型：
--
作者：
Graham, M B;Braciale, T J
在对大多数病毒的适应性免疫反应中，免疫系统的细胞和体液臂在清除病毒和感染病毒的细胞以及促进恢复方面发挥着互补的作用。为了评估CD4+和CD8+效应T淋巴细胞在病毒清除和恢复中的相对贡献，我们研究了B淋巴细胞缺陷小鼠对致死性A型流感病毒感染的宿主反应，并有针对性地打断了免疫球蛋白MU重链。我们的结果表明，幼稚的B细胞缺陷小鼠对致死性A型流感病毒感染的易感性是野生型小鼠的50-100倍。然而，在接种了亚致死剂量的流感后，免疫B细胞缺陷的动物对致命病毒感染的抵抗力增强了。这一发现表明，对致死性病毒攻击的抵抗力增加的原因是抗体非依赖性的免疫介导的抗病毒机制。为了评估流感特异性CD4+和CD8+效应T细胞在这一过程中的作用，我们将特定克隆群体的流感特异性CD4+和CD8+效应T细胞过继转移到致死性感染的B细胞缺陷小鼠体内。克隆的CD8+效应器有效地促进了致命感染的恢复，而克隆的CD4+T细胞只提供了部分保护。这些结果表明，记忆T淋巴细胞可以独立于体液免疫反应发挥作用，以便在免疫个体中增强对流感感染的抵抗力。讨论了这些结果对预防人类流感感染疫苗接种的潜在影响。
In the adaptive immune response to most viruses, both the cellular and humoral arms of the immune system play complementary roles in eliminating virus and virus-infected cells and in promoting recovery. To evaluate the relative contribution of CD4+ and CD8+ effector T lymphocytes in virus clearance and recovery, we have examined the host response to lethal type A influenza virus infection in B lymphocyte–deficient mice with a targeted disruption in the immunoglobulin mu heavy chain. Our results indicate that naive B cell–deficient mice have a 50– 100-fold greater susceptibility to lethal type A influenza virus infection than do wild type mice. However, after priming with sublethal doses of influenza, immune B cell–deficient animals show an enhanced resistance to lethal virus infection. This finding indicates that an antibody-independent immune-mediated antiviral mechanism accounts for the increased resistance to lethal virus challenge. To assess the contribution of influenza-specific CD4+ and CD8+ effector T cells in this process, defined clonal populations of influenza-specific CD4+ and CD8+ effector T cells were adoptively transferred into lethally infected B cell–deficient mice. Cloned CD8+ effectors efficiently promoted recovery from lethal infection, whereas cloned CD4+ T cells conferred only partial protection. These results suggest that memory T lymphocytes can act independently of a humoral immune response in order to confer resistance to influenza infection in immune individuals. The potential implications of these results for vaccination against human influenza infection are discussed.