Interleukin 12 and B7/CD28 interaction synergistically upregulate interleukin 10 production by human T cells.
Interleukin 12 (IL-12) is a heterodimeric cytokine which promotes the development of Th1 cells and their interferon gamma (IFN-gamma) production after TCR/CD3 triggering. Previous reports indicate that IL-12 synergizes with accessory signalling through B7/CD28 interaction in inducing proliferation and IFN-gamma production by human T cells. In this study, we investigated the capacity of IL-12 to modify cytokine synthesis by freshly purified human peripheral blood T cells stimulated with anti-CD3 as the primary signal and with CD80 on transfected mouse cells as an accessory signal. Our data demonstrate that IL-12 indeed synergizes with B7/CD28 interaction, not only in inducing IFN-gamma production, but also in enhancing IL-10 synthesis in a dose-dependent manner. In contrast, IL-4 and IL-5 production were slightly inhibited by IL-12. The effect of IL-12 on the secretion of IL-10 was confirmed by stimulating T cells in the absence of accessory cells with immobilized anti-CD3 mAb and soluble anti-CD28 mAb. CD80 and IL-12 mainly costimulated CD4+CD45RO+ T cells but not CD8+ or CD45RA+ T cells to produce IL-10. Cyclosporin A (CsA) partially inhibited, and a neutralizing anti-IL-2 mAb in combination with anti-IL-2R mAbs (anti-Tac and Mik beta1) strongly reduced IL-10 production. On the other hand, IL-12 did not affect IL-2 production. The data thus suggest a model in which optimal IL-10 production by stimulated peripheral blood T cells results from the co-operation of IL-12, B7/CD28 interaction and the ensuing IL-2 activity.
Peng
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X
Department of Pathophysiology, Faculty of medicine, Catholic University of Leuven, Belgium.
Kasran
A
A
Ceuppens
J L
JL
D000328:Adult; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018122:B7-1 Antigen; D018106:CD28 Antigens; D007376:Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D017493:Leukocyte Common Antigens