Type I interferon potentiates T-cell receptor mediated induction of IL-10-producing CD4+ T cells

Type I interferons (IFNs) have the dual ability to promote the development of the immune response and exert an anti-inflammatory activity. We analyzed the integrated effect of IFN-, TCR signal strength, and CD28 costimulation on human CD4(+) T-cell differentiation into cell subsets producing the anti- and proinflammatory cytokines IL-10 and IFN-. We show that IFN- boosted TCR-induced IL-10 expression in activated peripheral CD45RA(+)CD4(+) T cells and in whole blood cultures. The functional cooperation between TCR and IFN- efficiently occurred at low engagement of receptors. Moreover, IFN- rapidly cooperated with anti-CD3 stimulation alone. IFN-, but not IL-10, drove the early development of type I regulatory T cells that were mostly IL-10(+) Foxp3(-) IFN-(-) and favored IL-10 expression in a fraction of Foxp3(+) T cells. Our data support a model in which IFN- costimulates TCR toward the production of IL-10 whose level can be amplified via an autocrine feedback loop.