Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: Protective and deleterious effects

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

Research output: Contribution to journalArticle

207 Scopus citations

Abstract

Tumor necrosis factor (TNF, TNFα) 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.

Original languageEnglish (US)
Pages (from-to)93-104
Number of pages12
JournalImmunity
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Grivennikov, S. I., Tumanov, A. V., Liepinsh, D. J., Kruglov, A. A., Marakusha, B. I., Shakhov, A. N., Murakami, T., Drutskaya, L. N., Förster, I., Clausen, B. E., Tessarollo, L., Ryffel, B., Kuprash, D. V., & Nedospasov, S. A. (2005). Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils: Protective and deleterious effects. Immunity, 22(1), 93-104. https://doi.org/10.1016/j.immuni.2004.11.016