Graham M B, Braciale T J
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
J Exp Med. 1997 Dec 15;186(12):2063-8. doi: 10.1084/jem.186.12.2063.
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.
在针对大多数病毒的适应性免疫反应中，免疫系统的细胞免疫和体液免疫分支在清除病毒及病毒感染细胞以及促进恢复方面发挥着互补作用。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，我们研究了免疫球蛋白μ重链靶向破坏的B淋巴细胞缺陷小鼠对致死性甲型流感病毒感染的宿主反应。我们的结果表明，与野生型小鼠相比，天然B细胞缺陷小鼠对致死性甲型流感病毒感染的易感性高50至100倍。然而，用亚致死剂量的流感病毒进行预刺激后，免疫B细胞缺陷动物对致死性病毒感染的抵抗力增强。这一发现表明，一种不依赖抗体的免疫介导抗病毒机制导致了对致死性病毒攻击抵抗力的增强。为了评估甲型流感特异性CD4⁺和CD8⁺效应T细胞在此过程中的作用，将特定克隆群体的甲型流感特异性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⁺效应细胞有效地促进了从致死性感染中的恢复，而克隆的CD4⁺T细胞仅提供部分保护。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，从而使免疫个体对流感感染具有抵抗力。本文讨论了这些结果对人类流感感染疫苗接种的潜在意义。
