TL1A Synergizes with IL-12 and IL-18 to Enhance IFN-gamma Production in Human T Cells and NK Cells

摘要

TL1A,a recently described TNF-like cytokine that interacts with DR3,costimulates T cells and augments anti-CD3 plus anti-CD28 IFN-gamma production.In the current study we show that TL1A or an agonistic anti-DR3 mAb synergize with IL-12/IL-18 to augment IFN-gamma production in human peripheral blood T cells and NK cells.TL1A also enhanced IFN-y production by IL-12/IL-18 stimulated CD56~+T cells.When expressed as fold change,the synergistic effect of TL1A on cytokine-induced IFN-y production was more pronounced on CD4~+and CD8~+T cells than on CD56~+T cells or NK cells.Intracellular cytokine staining showed that TL1A significantly enhanced both the percentage and the mean fluorescence intensity of IFN-y-producing T cells in response to IL-12/IL-18.The combination of IL-12 and IL-18 markedly up-regulated DR3 expression in NK cells,whereas it had minimal effect in T cells.Our data suggest that TL1A/DR3 pathway plays an important role in the augmentation of cytokine-induced IFN-y production in T cells and that DR3 expression is differentially regulated by IL-12/IL-18 in T cells and NK cells.