Activation of virus-specific CD8+ T cells by lipopolysaccharide-induced IL-12 and IL-18
Activation of virus-specific CD8+ T cells by lipopolysaccharide-induced IL-12 and IL-18
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DOI：
10.4049/jimmunol.173.11.6873
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发表时间：
2004-12-01
影响因子：
4.4
通讯作者：
Slifka, MK
中科院分区：
文献类型：
--
作者：
Raué, HP;Brien, JD;Slifka, MK
病毒特异性 T 细胞代表了 Ag 特异性、适应性免疫的标志。然而，一些T细胞也表现出先天功能，包括响应LPS等微生物产物或暴露于IL-12和/或IL-18而产生非Ag特异性IFN-γ。在这些研究中，我们直接离体检查了LPS诱导的CD8+T细胞的细胞因子反应。急性病毒感染后，70-80% 的病毒特异性 T 细胞在接触 LPS 诱导的细胞因子后会产生 IFN-γ，中和实验表明这几乎完全是通过产生 IL-12 和 IL-18 来介导的。这些细胞因子的不同组合表明，IL-12 降低了 IL-18 激活 T 细胞的阈值，为 IL-12/IL-18 协同作用提供了新的视角。此外，记忆T细胞表现出高IL-18R表达，并对IL-12和IL-18的组合有效做出反应，但不能单独对IL-18作出反应，即使在高细胞因子浓度下也是如此。这表明，IL-12 和 IL-18 在触发记忆 T 细胞产生 IFN-γ 方面的协同作用不仅仅是由于 IL-18 表面受体的上调，如之前在初始 T 细胞中所显示的那样。总之，这些研究表明，病毒特异性 T 细胞如何能够在不相关的微生物感染期间弥合先天免疫和适应性免疫之间的差距，同时试图保护宿主免受细胞因子诱导的免疫病理学和内毒素休克的影响。
Virus-specific T cells represent a hallmark of Ag-specific, adaptive immunity. However, some T cells also demonstrate innate functions, including non-Ag-specific IFN-gamma production in response to microbial products such as LPS or exposure to IL-12 and/or IL-18. In these studies we examined LPS-induced cytokine responses of CD8(+) T cells directly ex vivo. Following acute viral infection, 70-80% of virus-specific T cells will produce IFN-gamma after exposure to LPS-induced cytokines, and neutralization experiments indicate that this is mediated almost entirely through production of IL-12 and IL-18. Different combinations of these cytokines revealed that IL-12 decreases the threshold of T cell activation by IL-18, presenting a new perspective on IL-12/IL-18 synergy. Moreover, memory T cells demonstrate high IL-18R expression and respond effectively to the combination of IL-12 and IL-18, but cannot respond to IL-18 alone, even at high cytokine concentrations. This demonstrates that the synergy between IL-12 and IL-18 in triggering IFN-gamma production by memory T cells is not simply due to up-regulation of the surface receptor for IL-18, as shown previously with naive T cells. Together, these studies indicate how virus-specific T cells are able to bridge the gap between innate and adaptive immunity during unrelated microbial infections, while attempting to protect the host from cytokine-induced immunopathology and endotoxic shock.