Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils:: Protective and deleterious effects
Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils:: Protective and deleterious effects
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DOI：
10.1016/j.immuni.2004.11.016
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发表时间：
2005-01-01
期刊：
影响因子：
32.4
通讯作者：
Nedospasov, SA
中科院分区：
文献类型：
--
作者：
Grivennikov, SI;Tumanov, AV;Nedospasov, SA
肿瘤坏死因子（TNF，TNF α）参与各种病理生理过程，可以是保护性的，如在宿主防御中，也可以是有害的，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的体内功能，我们产生了靶向各种白细胞亚群的TNF消融小鼠。全身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必不可少的，而T细胞来源的TNF对于保护免受高细菌负荷是重要的。此外，T细胞来源的TNF和巨噬细胞来源的TNF在促进自身免疫性肝炎中具有关键和非冗余的功能。我们的数据表明，T细胞特异性TNF消融可能提供优于全身阻断的治疗优势。
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.