Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha.
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-regul...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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1997
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| _version_ | 1797078922993598464 |
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| author | Parry, S Sebbag, M Feldmann, M Brennan, F |
| author_facet | Parry, S Sebbag, M Feldmann, M Brennan, F |
| author_sort | Parry, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:38:27Z |
| format | Journal article |
| id | oxford-uuid:82384411-e31a-4285-b164-1814a12cc109 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:38:27Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:82384411-e31a-4285-b164-1814a12cc1092022-03-26T21:35:51ZContact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:82384411-e31a-4285-b164-1814a12cc109EnglishSymplectic Elements at Oxford1997Parry, SSebbag, MFeldmann, MBrennan, FIL-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. |
| spellingShingle | Parry, S Sebbag, M Feldmann, M Brennan, F Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. |
| title | Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. |
| title_full | Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. |
| title_fullStr | Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. |
| title_full_unstemmed | Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. |
| title_short | Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. |
| title_sort | contact with t cells modulates monocyte il 10 production role of t cell membrane tnf alpha |
| work_keys_str_mv | AT parrys contactwithtcellsmodulatesmonocyteil10productionroleoftcellmembranetnfalpha AT sebbagm contactwithtcellsmodulatesmonocyteil10productionroleoftcellmembranetnfalpha AT feldmannm contactwithtcellsmodulatesmonocyteil10productionroleoftcellmembranetnfalpha AT brennanf contactwithtcellsmodulatesmonocyteil10productionroleoftcellmembranetnfalpha |