Inhibition by IL-12 and IFN-α of I-309 and macrophage-derived chemokine production upon TCR triggering of human Th1 cells

Andrea Iellem, Lucia Colantonio, Sunil Bhakta, Silvano Sozzani, Alberto Mantovani, Francesco Sinigaglia, Daniele D'Ambrosio

Research output: Contribution to journalArticlepeer-review

Abstract

Th1 and Th2 cells, which produce distinct sets of cytokines, differentially express several chemokine receptors that may regulate their tissue-specific localization. Although the expression pattern and regulation of chemokines are likely to play a critical role in many immunopathological processes, they remain largely unknown. Here, we investigated the requirements for Th1 and Th2 cells to produce the Th2 cell-attracting chemokines thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and I-309. TCR triggering of Th1 and Th2 cells leads to production of MDC and I-309 (CCR4 and CCR8 ligands, respectively), whereas TARC (CCR4 ligand) is selectively produced by Th2 cells. Secretion of these chemokines appears to be independent of endogenous production of IL-4 and IFN-γ. IL-12 and IFN-α, cytokines that promote the differentiation of human Th1 cells, selectively inhibit secretion and mRNA expression of MDC and I-309 by Th1 cells. Suppression of I-309 secretion results in a decreased chemotactic effect on L1.2 cells transfected with human CCR8, indicating that IL-12 and IFN-α may inhibit the recruitment of CCR8-expressing cells such as Th2 cells. The inhibition of Th2 cell-attracting chemokines MDC and I-309 illustrates a novel mechanism by which IL-12 and IFN-α could promote and maintain an ongoing Th1 response.

Original languageEnglish
Pages (from-to)1030-1039
Number of pages10
JournalEuropean Journal of Immunology
Volume30
Issue number4
Publication statusPublished - 2000

Keywords

  • Chemokine
  • Cytokine
  • Inflammation
  • Lymphocyte homing
  • Th1/Th2

ASJC Scopus subject areas

  • Immunology

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