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NLM AIDSLINE

IL-10 inhibits nuclear factor-kappa B/Rel nuclear activity in CD3-stimulated human peripheral T lymphocytes.




 

J Immunol. 1996 Mar 15;156(6):2119-23. Unique Identifier : AIDSLINE

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.

Antigens, CD3/*IMMUNOLOGY Base Sequence Dose-Response Relationship, Immunologic Down-Regulation (Physiology)/IMMUNOLOGY Human Interleukin-10/*PHARMACOLOGY Leukocytes, Mononuclear/DRUG EFFECTS/IMMUNOLOGY/METABOLISM *Lymphocyte Transformation/DRUG EFFECTS Molecular Sequence Data Monocytes/IMMUNOLOGY Muromonab-CD3/PHARMACOLOGY NF-kappa B/*ANTAGONISTS & INHIB/BIOSYNTHESIS Support, Non-U.S. Gov't T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY/*METABOLISM Tetradecanoylphorbol Acetate/PHARMACOLOGY JOURNAL ARTICLE



 




Information in this article was accurate in October 30, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.