Lawrence B Paige, Vorderstrasse Beth A
Department of Pharmaceutical Sciences, Pharmacology/Toxicology Program, College of Pharmacy, Washington State University, Pullman, Washington 99164-6534, USA.
Toxicol Sci. 2004 Jun;79(2):304-14. doi: 10.1093/toxsci/kfh094. Epub 2004 Feb 19.
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.
尽管芳烃受体（AhR）配体对初次免疫反应的抑制作用已广为人知，但很少有研究明确考察AhR激动剂对免疫记忆的影响。因此，本研究的目的是表征暴露于最强效AhR配体2,3,7,8-四氯二苯并对二恶英（TCDD）的小鼠对流感病毒的回忆反应。给小鼠单次注射TCDD，其导致初次反应受到抑制，并监测对同型感染的回忆抗体和CD8(+) T细胞反应的动力学。初次感染后两到三个月，用TCDD处理的小鼠中病毒特异性IgG水平受到抑制，再次感染后仍保持抑制状态。相比之下，TCDD处理组的IgA水平有所升高。病毒特异性CD8(+) T细胞的回忆反应也受到抑制，因为病毒特异性记忆CD8(+) T细胞数量减少，且回忆反应的动力学延迟。在载体处理或TCDD处理的小鼠中均未观察到发病或死亡情况，两组小鼠在再次感染后三天内均清除了病毒。因此，关于理解初次免疫反应期间AhR的激活如何影响免疫记忆的产生，我们的数据呈现出一个复杂的情况。一方面，TCDD处理降低了初次反应，导致病毒特异性IgG水平降低以及记忆CD8库减少。然而，对同型感染的二次反应对宿主仍具有保护作用。这些发现对于确定AhR配体对淋巴细胞功能产生不利影响的机制以及理解控制免疫记忆获得的机制具有重要意义。
