T细胞和巨噬细胞/中性粒细胞产生的肿瘤坏死因子在体内具有独特且非冗余的功能：保护作用和有害作用。

Distinct and nonredundant in vivo functions of TNF produced by t cells and macrophages/neutrophils: protective and deleterious effects.

作者信息

Grivennikov Sergei I, Tumanov Alexei V, Liepinsh Dmitry J, Kruglov Andrei A, Marakusha Boris I, Shakhov Alexander N, Murakami Takaya, Drutskaya Ludmila N, Förster Irmgard, Clausen Björn E, Tessarollo Lino, Ryffel Bernhard, Kuprash Dmitry V, Nedospasov Sergei A

机构信息

Laboratory of Molecular Immunology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences and Belozersky Institute of Physico-Chemical Biology, 32 Vavilov Str., 119991 Moscow, Russia.

出版信息

Immunity. 2005 Jan;22(1):93-104. doi: 10.1016/j.immuni.2004.11.016.

DOI:10.1016/j.immuni.2004.11.016

PMID:15664162

Abstract

Tumor necrosis factor (TNF, TNFalpha) is implicated in various pathophysiological processes and can be either protective, as in host defense, or deleterious, as in autoimmunity or toxic shock. To uncover the in vivo functions of TNF produced by different cell types, we generated mice with TNF ablation targeted to various leukocyte subsets. Systemic TNF in response to lipopolysaccharide was produced mainly by macrophages and neutrophils. This source of TNF was indispensable for resistance to an intracellular pathogen, Listeria, whereas T-cell-derived TNF was important for protection against high bacterial load. Additionally, both T-cell-derived TNF and macrophage-derived TNF had critical and nonredundant functions in the promotion of autoimmune hepatitis. Our data suggest that T-cell-specific TNF ablation may provide a therapeutic advantage over systemic blockade.

摘要

肿瘤坏死因子（TNF，TNFα）参与多种病理生理过程，它既可以具有保护作用，如在宿主防御中，也可能有害，如在自身免疫或中毒性休克中。为了揭示不同细胞类型产生的TNF在体内的功能，我们构建了将TNF基因敲除靶向于各种白细胞亚群的小鼠。对脂多糖产生的全身性TNF主要由巨噬细胞和中性粒细胞产生。这种TNF来源对于抵抗细胞内病原体李斯特菌是不可或缺的，而T细胞衍生的TNF对于抵抗高细菌载量很重要。此外，T细胞衍生的TNF和巨噬细胞衍生的TNF在促进自身免疫性肝炎方面都具有关键且不可替代的作用。我们的数据表明，T细胞特异性TNF基因敲除可能比全身阻断具有治疗优势。