A minor population of splenic dendritic cells expressing CD19 mediates IDO-dependent T cell suppression via type I IFN signaling following B7 ligation

Babak Baban, Anna M. Hansen, Phillip R. Chandler, Anna Manlapat, Adam Bingaman, David J. Kahler, David H. Munn, Andrew L. Mellor

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

By ligating CD80/CD86 (B7) molecules, the synthetic immunomodulatory reagent CTLA4-Ig (soluble synthetic CTLA4 fusion protein) induces expression of the enzyme indoleamine 2,3-dioxygenase (IDO) in some dendritic cells (DCs), which acquire potent T cell regulatory functions as a consequence. Here we show that this response occurred exclusively in a population of splenic DCs co-expressing the marker CD19. B7 ligation induced activation of the transcription factor signal transducer and activator of transcription (STAT1) in sorted CD19+, but not CD19NEG, DCs. STAT1 activation occurred even when DCs lacked receptors for type II IFN (IFNγ); however, STAT1 activation and IDO up-regulation were not observed when DCs lacked receptors for type I IFN (IFNαβ). Thus, IFNα, but not IFNγ, signaling was essential for STAT1 activation and IDO up-regulation in CD19+ DCs following B7 ligation. Consistent with these findings, B7 ligation also induced sorted CD19+, but not CD19NEG, DCs to express IFNα. Moreover, recombinant IFNα induced CD19+, but not CD19NEG, DCs to mediate IDO-dependent T cell suppression, showing that IFNα signaling could substitute for upstream signals from B7. These data reveal that a minor population of splenic DCs expressing the CD19 marker is uniquely responsive to B7 ligation, and that IFNα-mediated STAT1 activation is an essential intermediary signaling pathway that promotes IDO induction in these DCs. Thus, CD19+ DCs may be a target for regulatory T cells expressing surface CTLA4, and may suppress T cell responses via induction of IDO.

Original languageEnglish (US)
Pages (from-to)909-919
Number of pages11
JournalInternational Immunology
Volume17
Issue number7
DOIs
StatePublished - Jul 1 2005

Keywords

  • CTLA4-lg
  • Dendritic cells
  • I cell suppression
  • Interferon
  • STAT1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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