TL1A synergizes with IL-12 and IL-18 to enhance IFN-γ production in human T cells and NK cells

被引:122
作者
Papadakis, KA
Prehn, JL
Landers, C
Han, QW
Luo, X
Cha, SC
Wei, P
Targan, SR
机构
[1] Cedar Sinai Inflammatory Bowel Dis Ctr, Los Angeles, CA 90048 USA
[2] Human Genome Sci, Rockville, MD 20850 USA
关键词
D O I
10.4049/jimmunol.172.11.7002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
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-gamma production by IL-12/IL-18 stimulated CD56(+) T cells. When expressed as fold change, the synergistic effect of TL1A on cytokine-induced IFN-gamma 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-gamma-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-gamma production in T cells and that DR3 expression is differentially regulated by IL-12AL-18 in T cells and NK cells.
引用
收藏
页码:7002 / 7007
页数:6
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