Pavić I, Polić B, Crnković I, Lucin P, Jonjić S, Koszinowski U H
Department of Physiology and Immunology, Faculty of Medicine, University of Rijeka, Croatia.
J Gen Virol. 1993 Oct;74 ( Pt 10):2215-23. doi: 10.1099/0022-1317-74-10-2215.
Interferon gamma (IFN gamma) represents an essential cytokine involved in murine cytomegalovirus (MCMV) clearance from the salivary gland and the control of horizontal transmission. Because IFN gamma cannot be responsible for all cytokine effects during recovery from MCMV infection we have now tested the potential participation of tumour necrosis factor alpha (TNF alpha) in the antiviral defence. Neutralization of endogenous TNF alpha abolished the antiviral activity of CD4 T cells in immunocompetent as well as in CD8 subset-deficient mice. These data suggest that the antiviral effect of the CD4 subset requires the presence of at least two cytokines, namely IFN gamma and TNF alpha. Depletion of endogenous TNF alpha in adoptive cell transfer recipients diminished the antiviral function of CD8 T lymphocytes suggesting that TNF alpha also participates in CD8 T cell effector functions. Furthermore, endogenous cytokines were found to be required for survival after infection with lethal doses of MCMV, whereas immunotherapy with recombinant TNF alpha and IFN gamma could not limit virus replication in vivo. The results suggest that, similar to IFN gamma, TNF alpha is an integral part of the protective mechanisms involved in cytomegalovirus clearance.
γ干扰素（IFNγ）是一种重要的细胞因子，参与从唾液腺清除小鼠巨细胞病毒（MCMV）以及控制水平传播。由于IFNγ不可能对MCMV感染恢复过程中的所有细胞因子效应负责，我们现在测试了肿瘤坏死因子α（TNFα）在抗病毒防御中的潜在参与情况。中和内源性TNFα消除了免疫健全小鼠以及CD8亚群缺陷小鼠中CD4 T细胞 的抗病毒活性。这些数据表明，CD4亚群的抗病毒作用至少需要两种细胞因子，即IFNγ和TNFα。在过继性细胞转移受体中耗尽内源性TNFα会减弱CD8 T淋巴细胞的抗病毒功能，这表明TNFα也参与CD8 T细胞效应功能。此外，发现内源性细胞因子是感染致死剂量MCMV后存活所必需的，而用重组TNFα和IFNγ进行免疫治疗无法在体内限制病毒复制。结果表明，与IFNγ类似，TNFα是参与巨细胞病毒清除的保护机制的一个组成部分。
