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J. Biol. Chem., Vol. 275, Issue 25, 19282-19287, June 23, 2000
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From INSERM U431, Microbiologie et Pathologie Cellulaire
Infectieuse, Université Montpellier 2, Place Eugène
Bataillon, cc 100, 34095 Montpellier cedex 05, France
Tumor necrosis factor-
Tumor Necrosis Factor-
Production Is Differently Regulated in
and 
Human T Lymphocytes*
,
(TNF-) plays a
crucial role in the early defense against pathogens. This cytokine is
produced by several cell types including T lymphocytes expressing the
as well as the 
T cell receptor (TcR). In human, the
circulating T cells, which mostly express V9V2 TcR, have
been strongly suggested to play an important protective role against
infectious agents. These activated cells early produce high amounts of
TNF-, which induce a determinant beneficial effect against
development of intracellular pathogens; however, sustained production
of this cytokine can result in immunopathological diseases. The signals that regulate TNF- production in V9V2 T cells are totally
unknown. In primary T cells, TNF- production was shown to
necessitate engagement of the TcR and CD28, and to be independent of
the p38 mitogen activated protein kinase pathway. We demonstrate herein that, in contrast to T cells, TNF- production in V9V2 T lymphocytes is independent of CD28 costimulation and highly dependent on TcR-induced p38 kinase and extracellular signal-regulated kinase 2 pathway activation for optimal cytokine release. Moreover, we bring
elements supporting the idea that the "activation threshold" of
T cells leading to cytokine production is lower than that of
T cells.
*
This work was supported by the Fondation Singer Polignac
(France).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 33-467-14-42-44;
Fax: 33-467-14-33-38; E-mail: favero@crit.univ-montp2.fr.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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