TY - JOUR
T1 - Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils
T2 - Protective and deleterious effects
AU - Grivennikov, Sergei I.
AU - Tumanov, Alexei V.
AU - Liepinsh, Dmitry J.
AU - Kruglov, Andrei A.
AU - Marakusha, Boris I.
AU - Shakhov, Alexander N.
AU - Murakami, Takaya
AU - Drutskaya, Ludmila N.
AU - Förster, Irmgard
AU - Clausen, Björn E.
AU - Tessarollo, Lino
AU - Ryffel, Bernhard
AU - Kuprash, Dmitry V.
AU - Nedospasov, Sergei A.
N1 - Funding Information:
This project has been funded in part by MCB grants from the Russian Academy of Sciences, Russian Foundation for Basic Research (grants 03-04-49097-a and 03-04-49083-a), and with US Federal funds from the National Cancer Institute, National Institutes of Health under Contract NO1-CO-12400. S.I.G. was supported by INTAS grant YSF 2002-0235. S.A.N. is International Research Scholar of the Howard Hughes Medical Institute.
PY - 2005/1
Y1 - 2005/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2004.11.016
DO - 10.1016/j.immuni.2004.11.016
M3 - Article
C2 - 15664162
AN - SCOPUS:19944432071
SN - 1074-7613
VL - 22
SP - 93
EP - 104
JO - Immunity
JF - Immunity
IS - 1
ER -