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The Journal of Immunology, 1998, 160: 4298-4304.
Copyright © 1998 by The American Association of Immunologists

Type I IFNs Inhibit Human Dendritic Cell IL-12 Production and Th1 Cell Development1

Bradford L. McRae*, Roshanak Tolouei Semnani*, Mark P. Hayes{dagger} and Gijs A. van Seventer2,*

* Committee on Immunology, Department of Pathology, Division of Biological Sciences, University of Chicago, Chicago, IL; and {dagger} Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD

We have investigated the role of type I IFNs (IFN-{alpha} and -ß) in human T cell differentiation using anti-CD3 mAb and allogeneic, in vitro-derived dendritic cells (DC) as APCs. DC were very efficient activators of naive CD4+ T cells, providing necessary costimulation and soluble factors to support Th1 differentiation and expansion. Addition of IFN-{alpha}ß to DC/T cell cultures resulted in induction of T cell IL-10 production and inhibition of IFN-{gamma}, TNF-{alpha}, and LT secretion. Diminished T cell IFN-{gamma} production correlated with IFN-{alpha}ß-mediated inhibition of the p40 chain of the IL-12 heterodimer secreted by DC. Suppression of p40 IL-12 and IFN-{gamma} was not due to increased levels of IL-10 in these cultures, and production of IFN-{gamma} could be restored by exogenous IL-12. These data indicate that type I IFNs inhibit DC p40 IL-12 expression, which is required for development of IFN-{gamma}-producing CD4+ T cells. Furthermore, when T cells were restimulated without IFN-ß, these cells induced less p40 IL-12 from DC, suggesting that the functional properties of T cells may regulate DC function. Thus, IFN-{alpha}ß inhibits both IL-12-dependent and independent Th1 cytokine production and provides a mechanism for inhibition of IL-12-mediated immunity in viral infections.




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