Baumgarth N, Kelso A
Cooperative Research Center for Vaccine Technology and Transplantation Biology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
J Virol. 1996 Jul;70(7):4411-8. doi: 10.1128/JVI.70.7.4411-4418.1996.
Influenza virus infection induces the local production of gamma interferon (IFN-gamma) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-gamma by using monoclonal antibodies. Neutralization of IFN-gamma led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum but had little effect on other isotypes. Studies on cells isolated from the lung parenchyma itself revealed that at the height of the immune response the ability of these cells to produce cytokines after antigen or T-cell receptor/CD3 stimulation was not affected. Ex vivo cytolytic activity by lung parenchyma cells, which is induced by infection with this virus in normal mice, was also found to be undisturbed by this treatment, even though anti-IFN-gamma antibody activity was recovered from lung lavage samples and sera at all days studied. Surprisingly, in vivo neutralization of IFN-gamma led to a significant reduction in the magnitude of the cellular infiltrate in the lung tissue which followed infection, suggesting an involvement of IFN-gamma in the mechanisms that regulate increased leucocyte traffic in the inflamed lung parenchyma. This conclusion was supported by findings of differences between mock-treated and anti-IFN-gamma-treated mice in the number of CD8+ lung T cells expressing CD49d (alpha4-integrin) and CD62L at various times after influenza virus infection. This study therefore demonstrates that IFN-gamma affects the local cellular response in the respiratory tract as well as the systemic humoral response to influenza virus infection.
流感病毒感染可诱导呼吸道中的T细胞和非T细胞局部产生γ干扰素（IFN-γ）。为阐明这种细胞因子的可能功能，我们使用单克隆抗体在体内中和或未中和IFN-γ的BALB/c小鼠中研究了对流感病毒的体液和局部细胞免疫反应。中和IFN-γ导致血清中病毒特异性免疫球蛋白G2a和G3的滴度显著降低，但对其他同种型影响很小。对从肺实质本身分离的细胞的研究表明，在免疫反应高峰期，这些细胞在抗原或T细胞受体/CD3刺激后产生细胞因子的能力未受影响。正常小鼠感染该病毒后诱导的肺实质细胞的体外溶细胞活性，也发现不受该处理的干扰，尽管在所有研究日都从肺灌洗样本和血清中检测到了抗IFN-γ抗体活性。令人惊讶的是，体内中和IFN-γ导致感染后肺组织中细胞浸润的程度显著降低，这表明IFN-γ参与了调节炎症肺实质中白细胞流量增加的机制。流感病毒感染后不同时间，在假处理和抗IFN-γ处理小鼠中表达CD49d（α4整合素）和CD62L的CD8+肺T细胞数量存在差异，这一发现支持了这一结论。因此这项研究表明，IFN-γ影响呼吸道中的局部细胞反应以及对流感病毒感染的全身体液反应。
