title: TL1A synergizes with IL-12 and IL-18 to enhance IFN-gamma production in human T cells and NK cells.
abstract: 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-12/IL-18 in T cells and NK cells.
authors.affiliation: Cedars-Sinai Inflammatory Bowel Disease Center, Los Angeles, CA 90048, USA.
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Papadakis
authors.forename: John L
authors.initials: JL
authors.lastname: Prehn
authors.forename: Carol
authors.initials: C
authors.lastname: Landers
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Han
authors.forename: Xia
authors.initials: X
authors.lastname: Luo
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Cha
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
mesh_terms: D019002:CD56 Antigen / Q000032:analysis; D004357:Drug Synergism; D015803:HLA-DR3 Antigen / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D019002:CD56 Antigen; D015803:HLA-DR3 Antigen; D020382:Interleukin-18; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma