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Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha.

S L Parry, M Sebbag, M Feldmann and F M Brennan
J Immunol April 15, 1997, 158 (8) 3673-3681;
S L Parry
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M Sebbag
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M Feldmann
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F M Brennan
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Abstract

IL-10, originally described as a cytokine synthesis inhibitory factor, is secreted by a number of cells of the immune system, including monocytes and T cells. IL-10 is a potent inhibitor of monocyte/macrophage activation, and we have shown previously this cytokine to be a major endogenous down-regulator of TNF-alpha in the rheumatoid joint. The mechanisms involved in regulating IL-10 production by cells of the monocyte/macrophage lineage are not yet clear, and most studies to date have used an exogenous triggering signal such as LPS. In this study, we have investigated the effects of cell-cell contact between human peripheral blood-derived activated T cells and monocytes in regulating monocyte IL-10 production. T cells, prestimulated with anti-CD3 mAb or with phorbol 12,13 di-butyrate and ionomycin, were fixed with glutaraldehyde and then incubated with monocytes. Fixed prestimulated T cells induced monocytes to secrete both IL-10 and TNF-alpha, and in addition, enhanced LPS-stimulated monocyte production of IL-10 and TNF-alpha in a dose-dependent manner. Stimulation of monocyte IL-10 production was abrogated when T cells were separated physically from monocytes within the tissue culture well. Using neutralizing Abs, we show that T cell contact-mediated induction of monocyte IL-10 is partially dependent on endogenous TNF-alpha and IL-1. Furthermore, T cell membrane TNF-alpha was shown to be one of the contact-mediated signals regulating monocyte IL-10 production. Endogenous IL-10 was shown to down-regulate T cell contact-mediated monocyte TNF-alpha production. Collectively, our results demonstrate that an autoregulatory loop exists involving both secreted and membrane-associated forms of IL-10 and TNF-alpha, and suggest that T cell-monocyte cognate interaction may play an important role in the regulation of monocyte cytokine production.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 8
15 Apr 1997
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Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha.
S L Parry, M Sebbag, M Feldmann, F M Brennan
The Journal of Immunology April 15, 1997, 158 (8) 3673-3681;

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Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha.
S L Parry, M Sebbag, M Feldmann, F M Brennan
The Journal of Immunology April 15, 1997, 158 (8) 3673-3681;
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Print ISSN 0022-1767        Online ISSN 1550-6606