1. IL-23 up-regulates IL-10 and induces IL-17 synthesis by polyclonally activated naive T cells in human.
- Author
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Vanden Eijnden S, Goriely S, De Wit D, Willems F, and Goldman M
- Subjects
- CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Humans, Interferon-gamma metabolism, Interleukin-23, Interleukin-23 Subunit p19, Recombinant Proteins metabolism, Interleukin-10 metabolism, Interleukin-17 metabolism, Interleukins metabolism, T-Lymphocytes metabolism
- Abstract
Interleukin (IL)-23 is a heterodimeric cytokine of the IL-12 family. Human IL-23 is known to induce interferon (IFN)-gamma production and proliferation in T cells, preferentially in the CD45RO+ memory subset. Yet, its role in the differentiation of human naive T cells remains largely unknown. We investigated the effect of recombinant human (rh)IL-23 on cord blood CD4+ and CD8+ T cells during polyclonal activation. The IL-23 receptor complex was not detectable in resting naive T cells. Nevertheless, both IL-23 receptor subunits, IL-12Rbeta1 and IL-23R, were rapidly induced after activation in both naive CD4+ and CD8+ T cells. In both cell types, rhIL-23 enhanced IFN-gamma production. This effect was demonstrable as early as 2 days after activation, illustrating that a functional IL-23 receptor is rapidly induced in naive T cells upon activation. In naive CD8+ T cells, rhIL-23 specifically induced the secretion of IL-17, a pro-inflammatory cytokine. Moreover, rhIL-23 significantly increased the production of IL-10 in both naive CD4+ and CD8+ T cells. IL-17 and IL-10 levels were not affected by the addition of rhIL-12. We conclude that IL-23 induces a specific cytokine profile, remarkably distinct from IL-12, in activated human naive T cells.
- Published
- 2005
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