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IL-10 inhibits nuclear factor-kappa B/Rel nuclear activity in CD3-stimulated human peripheral T lymphocytes.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1996 Mar 15; Vol. 156 (6), pp. 2119-23. - Publication Year :
- 1996
-
Abstract
- IL-10 markedly reduces nuclear factor (NF)-kappa B/Rel nuclear activity induced in PBMC by stimulation with the anti-CD3 mAb OKT3. The inhibition is exerted specifically on the NF-kappa B/Rel activation induced by mAb OKT3, and not that produced by PMA. As judged by supershifting the DNA-protein complexes with Abs recognizing specific components of the NF-kappa B/Rel protein family, the p50/p65 (Rel A) heterodimeric form of NF-kappa B is primarily affected. The maximal effect is observed at the IL-10 concentration of 20 U/ml. IL-10 inhibitory activity is exerted on T lymphocytes and is mediated by monocytes. Indeed, monocytes pretreated with IL-10 are able so inhibit NF-kappa B nuclear activity in purified T lymphocytes stimulated with OKT3. Soluble factors do not appear to be involved in the mechanism of inhibition. On the other hand, the up-regulation of CD80 Ag, found on monocytes obtained from PBMC incubated with OKT3, is not detected after addition of IL-10, and the anti-CD28 mAb CLB-CD28/1 restores the NF-kappa B/Rel nuclear activity in IL-10-inhibited lymphocytes. Therefore, the NF-kappa B/Rel inhibition might be ascribed to a lack of cooperation between accessory cells and T lymphocytes, resulting from down-regulation of a costimulatory molecule, such as CD80, produced by IL-10 on activated monocytes. Our results demonstrate that IL-10 can inhibit the induction of NF-kappa B/Rel nuclear activity in CD3-stimulated T lymphocytes. Since inappropriate activation of kappa B-driven genes has a physiopathologic role in a number of diseases, such as HIV infection, our findings support the possibility of using this cytokine to suppress an undesirable activation of these transcription factors.
- Subjects :
- Base Sequence
Dose-Response Relationship, Immunologic
Down-Regulation immunology
Humans
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
Molecular Sequence Data
Monocytes immunology
Muromonab-CD3 pharmacology
NF-kappa B biosynthesis
T-Lymphocytes drug effects
T-Lymphocytes immunology
Tetradecanoylphorbol Acetate pharmacology
CD3 Complex immunology
Interleukin-10 pharmacology
Lymphocyte Activation drug effects
NF-kappa B antagonists & inhibitors
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 156
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 8690900