4.5 Article

IL-12 synergizes with IL-18 or IL-1β for IFN-γ production from human T cells

Journal

INTERNATIONAL IMMUNOLOGY
Volume 12, Issue 2, Pages 151-160

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/intimm/12.2.151

Keywords

IL-12; IL-18; IL-1 beta; IFN-gamma; human T(h)1

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IL-18 is a proinflammatory cytokine that plays an important role in NK cell activation and T(h)1 response. IL-18 has a structural homology to IL-1, particularly IL-1 beta. IL-18R, composed of IL-1R-related protein (IL-18R alpha) and IL-1R accessory protein-like (IL-18R beta), belongs to the IL-1R family. Furthermore, IL-18R at least partly shares the signal transducing system with IL-1R, Thus, the IL-18-IL-18R system has a striking similarity to the IL-1-IL-1R system. For this reason, we regarded it important to investigate whether, like IL-18, IL-1 beta synergizes with IL-12 in inducing IFN-gamma production from human T cells and plays an important role in the T(h)1 response. Here we show that IL-12 and IL-1 beta synergistically induce T cells to proliferate and produce IFN-gamma without their TCR engagement. IL-12 stimulation induced an increase in the proportion of T cells positive for IL-18R, Then, IL-12-stimulated T cells responded to IL-18 or IL-1 beta by their proliferation and IFN-gamma production, although levels of IL-1 beta-induced responses were lower, CD4(+)CD45RA(+) T cells, although they constitutively expressed IL-18R beta mRNA, did not express IL-18R alpha mRNA, Phytohemagglutinin (PHA) stimulation alone induced IL-18R alpha mRNA without affecting the expression of IL-18R beta mRNA, T(h)1-inducing conditions (PHA, IL-12 and anti-IL-4) further increased this expression. We also show that T(h)1 cells but not T(h)2 cells have increased expression of IL-18R and IL-1R, and produce IFN-gamma in response to IL-18 and/or IL-1 beta.

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