The magnitude of CD4+ T cell recall responses is controlled by the duration of the secondary stimulus.
The magnitude of CD4+ T cell recall responses is controlled by the duration of the secondary stimulus.
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DOI：
10.4049/jimmunol.0900319
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Williams MA
中科院分区：
文献类型：
--
作者：
Ravkov EV;Williams MA
控制产生稳健的CD4+ T细胞回忆应答的参数仍然定义不清。在这项研究中，我们比较了再激发后CD4+和CD8+记忆T细胞的回忆反应。对淋巴细胞性脉络丛脑膜炎病毒（LCMV）或单核细胞增生李斯特菌免疫的小鼠进行同源再激发导致稳健的CD8+ T细胞回忆应答，但在同一宿主中CD4+ T细胞回忆应答的增强较差。相比之下，用仅共享CD4+ T细胞表位的病原体进行异源再激发导致CD4+ T细胞回忆应答的稳健加强。CD4+和CD8+ T细胞回忆应答的差异不能归因于对生长因子或APC的竞争，因为在用肽脉冲的树突状细胞再激发后可以同时诱导稳健的CD4+和CD8+ T细胞回忆应答。相反，CD4+ T细胞回忆应答取决于二次激发的持续时间。增加再激发剂量导致更有效地加强CD4+ T细胞回忆应答，并且人为地限制异源再激发后继发感染的持续时间不利地影响CD4+ T细胞而不是CD8+ T细胞回忆应答的大小。这些发现表明，同源再攻击后，通过次级CTL快速清除病原体阻止了CD4+ T细胞应答的最佳加强，因此在旨在促进CD4+ T细胞介导的保护的疫苗接种和加强策略的设计中具有重要的实际意义。
The parameters controlling the generation of robust CD4+ T cell recall responses remain poorly defined. In this study we compare recall responses by CD4+ and CD8+ memory T cells following rechallenge. Homologous rechallenge of mice immune to either lymphocytic choriomeningitis virus (LCMV) or Listeria monocytogenes results in robust CD8+ T cell recall responses but poor boosting of CD4+ T cell recall responses in the same host. In contrast, heterologous rechallenge with a pathogen sharing only a CD4+ T cell epitope results in robust boosting of CD4+ T cell recall responses. The disparity in CD4+ and CD8+ T cell recall responses cannot be attributed to competition for growth factors or APCs, as robust CD4+ and CD8+ T cell recall responses can be simultaneously induced following rechallenge with peptide-pulsed dendritic cells. Instead, CD4+ T cell recall responses are dependant on the duration of the secondary challenge. Increasing the rechallenge dose results in more potent boosting of CD4+ T cell recall responses, and artificially limiting the duration of secondary infection following heterologous rechallenge adversely impacts the magnitude of CD4+ T cell, but not CD8+ T cell, recall responses. These findings suggest that rapid pathogen clearance by secondary CTL following homologous rechallenge prevents optimal boosting of CD4+ T cell responses and therefore have important practical implications in the design of vaccination and boosting strategies aimed at promoting CD4+ T cell-mediated protection.
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