IL-10 INHIBITS NUCLEAR FACTOR-KAPPA-B REL NUCLEAR ACTIVITY IN CD3-STIMULATED HUMAN PERIPHERAL T-LYMPHOCYTES/

IL-10 markedly reduces nuclear factor (NF)-kappa B/Rel nuclear activit y induced in PBMC by stimulation with the anti-CD3 mAb OKT3. The inhib ition is exerted specifically on the NF-kappa B/Rel activation induced by mAb OKT3, and not on that produced by PMA. As judged by supershift ing the DNA-protein complexes with Abs recognizing specific components of the NF-kappa B/Rel protein family, the p50/p65 (Rel A) heterodimer ic form of NF-kappa B is primarily affected. The maximal effect is obs erved at the IL-10 concentration of 20 U/ml. IL-10 inhibitory activity is exerted on T lymphocytes and is mediated by monocytes. Indeed, mon ocytes pretreated with IL-10 are able to inhibit NF-KB nuclear activit y in purified T lymphocytes stimulated with OKT3. Soluble factors do n ot appear to be involved in the mechanism of inhibition. On the other hand, the up-regulation of CD80 Ag, found on monocytes obtained from P BMC 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 activ ity in IL-10-inhibited lymphocytes. Therefore, the NF-kappa B/Rel inhi bition might be ascribed to a lack of cooperation between accessory ce lls and T lymphocytes, resulting from down-regulation of a costimulato ry molecule, such as CD80,produced by IL-10 on activated monocytes, Ou r results demonstrate that IL-10 can inhibit the induction of NF-kappa B/Rel nuclear activity in CD3-stimulated T lymphocytes. Since inappro priate activation of KB-driven genes has a physiopathologic role in a number of diseases, such as HIV infection, our findings support the po ssibility of using this cytokine to suppress an undesirable activation of these transcription factors.