Interferon-β enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: Relevance for the immune modulatory effect in multiple sclerosis

Bettina Schreiner, Meike Mitsdoerffer, Bernd C. Kieseier, Lieping Chen, Hans Peter Hartung, Michael Weller, Heinz Wiendl

Research output: Contribution to journalArticle

Abstract

Antigen-presenting cells (APC) are considered to play a critical role in promoting the (re)activation of potentially autoreactive T cells in multiple sclerosis (MS), an inflammatory demyelinating disorder of the central nervous system (CNS). B7-H1 (PD-L1) is a novel member of the B7 family proteins which exert costimulatory and immune regulatory functions. Here we characterize the expression and functional activity of B7-H1 expressed on monocytes and dendritic cells (DC) of healthy donors and MS patients. B7-H1 is constitutively expressed on monocytes and differentially matured DC, but not on B cells. IFN-β, the principle immune modulatory agent used for the treatment of MS, strongly enhances B7-H1 expression on monocytes and semi-matured DC, but not B cells, in vitro. Importantly, B7-H1 expressed on APC strongly inhibits autologous CD4 T-cell activation. Neutralization of B7-H1 on monocytes or differentially matured monocyte-derived DC markedly increases the secretion of the pro-inflammatory cytokines, IFN-γ and IL-2, T-cell proliferation, and the expression of T-cell activation markers. B7-H1 exhibits strong inhibitory effects when expressed on monocytes, immature or semi-mature DC, but less so when expressed on fully matured DC. B7-H1-dependent immune inhibition is in part mediated by CD4/CD25+ regulatory T cells. There is no difference in the baseline expression levels of monocytic B7-H1 between untreated MS patients and healthy donors. However, both groups show a significant concentration-dependent up-regulation of B7-H1 mRNA and protein in response to IFN-β in vitro. Serial measurements of B7-H1 mRNA in MS patients before and 6 months after initiation of IFN-β therapy corroborated the relevance of these results in vivo: Nine of nine patients showed a significant increase in B7-H1 mRNA levels after 6 months of IFN-β therapy (median 1.04 vs. 8.78; p

Original languageEnglish (US)
Pages (from-to)172-182
Number of pages11
JournalJournal of Neuroimmunology
Volume155
Issue number1-2
DOIs
StatePublished - Oct 2004
Externally publishedYes

Keywords

  • Antigen-presenting cells
  • B7-family of costimulatory molecules
  • B7-H1
  • Costimulation
  • Interferon-β
  • Multiple sclerosis
  • Tolerogenic cells

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

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