Activation of the aryl hydrocarbon receptor diminishes the memory response to homotypic influenza virus infection but does not impair host resistance
Activation of the aryl hydrocarbon receptor diminishes the memory response to homotypic influenza virus infection but does not impair host resistance
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DOI：
10.1093/toxsci/kfh094
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发表时间：
2004-06-01
影响因子：
3.8
通讯作者：
Vorderstrasse, BA
中科院分区：
文献类型：
--
作者：
Lawrence, BP;Vorderstrasse, BA
虽然芳香烃受体（AhR）配体抑制原发性免疫应答是众所周知的，很少有研究明确检查AhR激动剂对免疫记忆的影响。因此，本研究的目的是描述小鼠暴露于最有效的AhR配体2，3，7，8-四氯二苯并对二恶英（TCDD）时对流感病毒的回忆反应。给小鼠单剂量的TCDD，这导致抑制的主要反应，回忆抗体和CD 8（+）T细胞反应的同型感染的动力学进行了监测。初次感染后两到三个月，用TCDD治疗的小鼠的病毒特异性IgG水平受到抑制，并且在再次感染后仍然受到抑制。相反，伊加水平在TCDD治疗组中增强。病毒特异性CD 8（+）T细胞的回忆反应也受到抑制，因为病毒特异性记忆CD 8（+）T细胞的数量减少，回忆反应的动力学延迟。在媒介物或TCDD处理的小鼠中没有观察到发病率或死亡率，并且两组小鼠在再感染后三天内清除了病毒。因此，关于理解初级免疫应答期间AhR的激活如何影响免疫记忆的产生，我们的数据呈现了一个复杂的故事。一方面，TCDD治疗降低了原发性应答，导致病毒特异性IgG水平降低和记忆性CD 8库减少。然而，对同型感染的继发反应仍然是宿主保护性的。这些发现对确定AhR配体对淋巴细胞功能产生不利影响的机制和理解控制免疫记忆获得的机制具有意义。
Although suppression of a primary immune response by aryl hydrocarbon receptor (AhR) ligands is well known, few studies have explicitly examined the effects of AhR agonists on immunological memory. Therefore, the goal of this study was to characterize the anamnestic response to influenza virus in mice exposed to the most potent AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice were given a single dose of TCDD, which caused suppression of the primary response, and kinetics of the recall antibody and CD8(+) T cell responses to homotypic infection were monitored. Two to three months after primary infection, virus-specific IgG levels were suppressed in mice treated with TCDD, and remained suppressed after reinfection. In contrast, IgA levels were enhanced in the TCDD-treated group. The recall response of virus-specific CD8(+) T cells was also suppressed, as the number of virus-specific memory CD8(+) T cells was diminished, and the kinetics of the recall response was delayed. No morbidity or mortality was observed in vehicle- or TCDD-treated mice, and mice in both groups cleared the virus within three days after reinfection. Thus, with regard to understanding how activation of the AhR during a primary immune response affects the generation of immunological memory, our data present a mixed story. On one hand, TCDD treatment reduced the primary response, resulting in lower levels of virus-specific IgG and diminution of the memory CD8 pool. However, the secondary response to homotypic infection was nevertheless host-protective. These findings have implications for determining the mechanisms by which AhR ligands adversely affect lymphocyte function and understanding the mechanisms that control the acquisition of immunological memory.