Vaccination with DNA encoding internal proteins of influenza virus does not require CD8+ cytotoxic T lymphocytes:: either CD4+ or CD8+ T cells can promote survival and recovery after challenge
Vaccination with DNA encoding internal proteins of influenza virus does not require CD8+ cytotoxic T lymphocytes:: either CD4+ or CD8+ T cells can promote survival and recovery after challenge
复制标题
DOI：
10.1093/intimm/12.1.91
复制
发表时间：
2000-01-01
影响因子：
4.4
通讯作者：
Subbarao, K
中科院分区：
文献类型：
--
作者：
Epstein, SL;Stack, A;Subbarao, K
DNA疫苗接种提供了在宿主细胞内表达病毒基因的优点，而没有传染性病毒的风险。像病毒疫苗一样，编码内部流感病毒蛋白的DNA疫苗可以诱导对保守表位的免疫，因此可以保护宿主免受多种病毒变异的侵害。CD8（+）细胞毒性T淋巴细胞（CTL）被描述为流感核蛋白（NP）保护的基本效应者，尽管CD4（+）细胞的作用较小。我们用编码流感病毒NP和基质(M)的质粒免疫小鼠。NP + M DNA允许B6小鼠在其他致命的挑战感染中存活，但不能保护CD8(+) CTL缺陷的bg - β (2) M（-/-）小鼠。然而，这并不能证明CTL是必需的，因为β (2)m（-/-）小鼠有多种免疫异常。我们在体内使用急性T细胞耗竭来识别防御挑战感染的关键效应物。由于肺淋巴细胞与病毒清除有关，因此在衰竭动物中分析了肺淋巴细胞的表面表型和细胞溶解活性，并进行了致死挑战研究。在NP + M dna免疫的BALB/c小鼠中，CD4（+）或CD8(+) T细胞在刺激期的消耗并没有显著降低生存率，而CD4+和CD8（+）细胞的同时消耗或所有CD90（+）细胞的消耗完全消除了生存率。我们得出结论，NP + M DNA疫苗接种诱导的T细胞免疫负责免疫防御，但CD8(+) T细胞在对这种疫苗接种的主动反应中不是必需的。CD4（+）或CD8(+) T细胞都可以在缺乏其他亚群的情况下促进生存和恢复。
DNA vaccination offers the advantages of viral gene expression within host cells without the risks of infectious virus. Like viral vaccines, DNA vaccines encoding internal influenza virus proteins can induce immunity to conserved epitopes and so may defend the host against a broad range of viral variants, CD8(+) cytotoxic T lymphocytes (CTL) have been described as essential effecters in protection by influenza nucleoprotein (NP), although a lesser role of CD4(+) cells has been reported. We immunized mice with plasmids encoding influenza virus NP and matrix (M). NP + M DNA allowed B6 mice to survive otherwise lethal challenge infection, but did not protect BG-beta(2)m(-/-) mice defective in CD8(+) CTL. However, this does not prove CTL are required, because beta(2)m(-/-) mice have multiple immune abnormalities. We used acute T cell depletion in vivo to identify effecters critical for defense against challenge infection. Since lung lymphocytes are relevant to virus clearance, surface phenotypes and cytolytic activity of lung lymphocytes were analyzed in depleted animals, along with lethal challenge studies. Depletion of either CD4(+) or CD8(+) T cells in NP + M DNA-immunized BALB/c mice during the challenge period did not significantly decrease survival, while simultaneous depletion of CD4+ and CD8(+) cells or depletion of all CD90(+) cells completely abrogated survival. We conclude that T cell immunity induced by NP + M DNA vaccination is responsible for immune defense, but CD8(+) T cells are not essential in the active response to this vaccination. Either CD4(+) or CD8(+) T cells can promote survival and recovery in the absence of the other subset.