Neff-LaFord Haley D, Vorderstrasse Beth A, Lawrence B Paige
Department of Pharmaceutical Sciences and the Pharmacology/Toxicology Graduate Program, College of Pharmacy, Washington State University, Pullman, WA 99164, USA.
Cell Immunol. 2003 Nov;226(1):54-64. doi: 10.1016/j.cellimm.2003.11.005.
Activation of the aryl hydrocarbon receptor (AhR) causes numerous defects in anti-viral immunity, including suppressed CTL generation and impaired host resistance. However, despite a reduced CTL response, mice that survive infection clear the virus. Therefore, we examined the contribution of NK cells and pro-inflammatory cytokines to viral clearance in influenza virus-infected mice exposed to TCDD, the most potent AhR agonist. Infection caused transient increases in pulmonary TNFalpha, IL-1, and IFNalpha/beta levels, but neither the kinetics nor magnitude of this response was affected by AhR activation. No IL-18 was detected at any time point examined. Exposure to TCDD enhanced NK cell numbers in the lung but did not affect their IFNgamma production. Furthermore, depletion of NK cells did not alter anti-viral cytolytic activity. In contrast, removal of CD8+ T cells ablated virus-specific cytolytic activity. These results demonstrate that the pulmonary CTL response to influenza virus is robust and few CTL are necessary for viral clearance.
芳烃受体（AhR）的激活会在抗病毒免疫中引发众多缺陷，包括细胞毒性T淋巴细胞（CTL）生成受抑制以及宿主抵抗力受损。然而，尽管CTL反应减弱，但存活下来的感染小鼠仍能清除病毒。因此，我们研究了自然杀伤细胞（NK细胞）和促炎细胞因子在接触2,3,7,8-四氯二苯并对二恶英（TCDD，最强效的AhR激动剂）的流感病毒感染小鼠中对病毒清除的作用。感染导致肺部肿瘤坏死因子α（TNFα）、白细胞介素-1（IL-1）和干扰素α/β（IFNα/β）水平短暂升高，但AhR激活既不影响该反应的动力学也不影响其幅度。在任何检测时间点均未检测到白细胞介素-18（IL-18）。接触TCDD可增加肺内NK细胞数量，但不影响其γ干扰素（IFNγ）的产生。此外，NK细胞的耗竭并未改变抗病毒细胞溶解活性。相反，去除CD8 + T细胞则消除了病毒特异性细胞溶解活性。这些结果表明，肺部对流感病毒的CTL反应很强，并且病毒清除所需的CTL数量很少。
