Dominant Role for TL1A/DR3 Pathway in IL-12 plus IL-18-Induced IFN-γ Production by Peripheral Blood and Mucosal CCR9+ T Lymphocytes
作者： Konstantinos A. Papadakis , Daocheng Zhu , John L. Prehn , Carol Landers , Armine Avanesyan
DOI: 10.4049/JIMMUNOL.174.8.4985
关键词: Interleukin 18 、 Interleukin 12 、 Intestinal mucosa 、 Tumor necrosis factor alpha 、 Cytotoxic T cell 、 Cytokine 、 Interleukin 21 、 Biology 、 T cell 、 Molecular biology 、 Immunology
摘要: The TNF-like cytokine TL1A augments IFN-gamma production by anti-CD3 plus anti-CD28 and IL-12/IL-18-stimulated peripheral blood (PB) T cells. However, only a small subset of PB cells respond to stimulation with production. CCR9+ represent circulating mucosal cell characteristics Th1/Tr1 profile. In the current study, we show that enhanced TCR- or CD2/CD28-stimulated CCR9(+)CD4+ had most pronounced effect on augmenting IL-12/IL-18-primed both percentage mean fluorescence intensity in as assessed intracellular staining. IL-12 IL-18 up-regulated DR3 expression but negligible CCR9(-)CD4+ isolated from intestine showed 37- 105-fold enhancement when was added IL-12/IL18 combination. Cell membrane-expressed preferentially expressed cells, blocking anti-TL1A mAb inhibited cytokine-primed approximately 50%. Our data TL1A/DR3 pathway plays dominant role ultimate level cytokine-induced gut-homing could play an important Th1-mediated intestinal diseases, such Crohn's disease, where increased IL-12, IL-18, TL1A, converge inflamed mucosa.
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