Moran T M, Isobe H, Fernandez-Sesma A, Schulman J L
Department of Microbiology, Mount Sinai School of Medicine, New York 10029, USA.
J Virol. 1996 Aug;70(8):5230-5. doi: 10.1128/JVI.70.8.5230-5235.1996.
Two different subsets of T cells, Th1 and Th2 cells, have been demonstrated to secrete different profiles of cytokines and to influence various infections in different ways. Whereas cytokines secreted by Th1 cells, particularly gamma interferon, promote the generation of cell-mediated immunity, Th2 cells and their cytokines (interleukin-4 [IL-4], IL-5, IL-10, and IL-13) have been shown to function in recovery from parasitic infections and in antibody responses. In this study, we analyzed the effects of the dominant Th2 cytokine, IL-4, on immunity to virus infection. We assessed the effects of IL-4 on both secondary immune responses by an adoptive transfer assay and primary immune responses by in vivo treatment of influenza virus-infected mice with IL-4. The results demonstrated that IL-4 can function to inhibit antiviral immunity at both stages. We found that IL-4 treatment of sensitized cells during secondary stimulation in vitro had little effect on their ability to lyse virus-infected target cells in a 51Cr release assay. Nevertheless, the clearance of influenza A/PR/8/34 (H1N1) virus from the lungs of infected BALB/c mice was significantly delayed after the transfer of virus-specific T cells secondarily stimulated in the presence of IL-4 in comparison to virus clearance in recipients of cells stimulated in the absence of IL-4. In contrast to the adoptive transfer results, the treatment of PR8 virus-infected mice with IL-4 during primary infection greatly suppressed the generation of cytotoxic T-cell precursors, as assessed by secondary stimulation in vitro. In addition, culture supernatants of secondarily stimulated spleen cells from IL-4-treated mice contained significantly less gamma interferon and more IL-4 than did spleen cells from controls. More importantly, the treatment of mice with IL-4 resulted in an extremely significant delay in virus clearance. Thus, IL-4 can inhibit both primary and secondary antiviral immune responses.
已证实T细胞的两个不同亚群，即Th1细胞和Th2细胞，分泌不同的细胞因子谱，并以不同方式影响各种感染。Th1细胞分泌的细胞因子，特别是γ干扰素，可促进细胞介导免疫的产生，而Th2细胞及其细胞因子（白细胞介素-4 [IL-4]、IL-5、IL-10和IL-13）已显示在寄生虫感染的恢复和抗体反应中发挥作用。在本研究中，我们分析了主要的Th2细胞因子IL-4对病毒感染免疫的影响。我们通过过继转移试验评估了IL-4对二次免疫反应的影响，并通过用IL-4体内处理流感病毒感染的小鼠评估了其对初次免疫反应的影响。结果表明，IL-4在两个阶段均能抑制抗病毒免疫。我们发现，在体外二次刺激期间用IL-4处理致敏细胞，对其在51Cr释放试验中裂解病毒感染靶细胞的能力影响很小。然而，与在无IL-4刺激的细胞受体中的病毒清除情况相比，在有IL-4存在的情况下二次刺激的病毒特异性T细胞转移后，感染的BALB/c小鼠肺中甲型流感病毒A/PR/8/34（H1N1）的清除明显延迟。与过继转移结果相反，在初次感染期间用IL-4处理PR8病毒感染的小鼠，极大地抑制了细胞毒性T细胞前体的产生，这通过体外二次刺激评估得出。此外，与对照组的脾细胞相比，来自IL-4处理小鼠的二次刺激脾细胞的培养上清液中γ干扰素含量显著降低，IL-4含量更高。更重要的是，用IL-4处理小鼠导致病毒清除极其显著地延迟。因此，IL-4可抑制初次和二次抗病毒免疫反应。
