Contribution of virus-specific CD8+ cytotoxic T cells to virus clearance or pathologic manifestations of influenza virus infection in a T cell receptor transgenic mouse model

被引:165
作者
Moskophidis, D
Kioussis, D
机构
[1] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA
[2] Natl Inst Med Res, Lab Mol Immunol, London NW7 1AA, England
关键词
CD8(+) cytotoxic T lymphocytes; influenza A virus; T cell receptor-transgenic mice; interferon gamma; influenza viral pneumonia;
D O I
10.1084/jem.188.2.223
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The ability of influenza virus to evade immune surveillance by neutralizing antibodies (Abs) directed against its variable surface antigens provides a challenge to the development of effective vaccines. CD8(+) cytotoxic T lymphocytes (CTLs) restricted by class I major histocompatibility complex molecules are important in establishing immunity to influenza virus because they recognize internal viral proteins which are conserved between multiple viral strains. In contrast, protective Abs are strain-specific. However, the precise role of effector CD8(+) CTLs in protection from influenza virus infection, critical for understanding disease pathogenesis, has not been well defined. In transgenic mice with a very high frequency of antiinfluenza CTL precursors, but without protective Abs, CD8(+) CTLs conferred protection against low dose viral challenge, but exacerbated viral pathology and caused mortality at high viral dose. The data suggest a dual role for CD8(+) CTLs against influenza, which may present a challenge to the development of effective CTL vaccines. Effector mechanisms used by CD8(+) CTLs in orchestrating clearance of virus and recovery front experimental influenza infection, or potentiation of lethal pathology, are discussed.
引用
收藏
页码:223 / 232
页数:10
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