Cytosine-phosphate-guanosine-DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen-stimulated CD4-positive cells

Clin Exp Immunol. 2012 Jul;169(1):1-9. doi: 10.1111/j.1365-2249.2012.04585.x.

Abstract

Co-stimulatory molecules are important for regulating T cell activation and immune response. CD274 [programmed death ligand 1 (PD-L1), B7-H1] has emerged as an important immune modulator that can block T cell receptor signalling. We have investigated whether PD-L1 and other co-stimulatory ligands could be expressed in human B cells stimulated by cytosine-phosphate-guanosine (CpG)-DNA. CpG-DNA strongly induced the co-inhibitory molecule ligand, PD-L1, of human B cells. Results show that nuclear factor-kappa B (NF-κB) signalling is involved directly in CpG-DNA-induced PD-L1 expression in human B cells. We sought to determine the effect of CpG-DNA-treated B cells on T helper type 2 (Th2) cytokine production in Cry j 1 (Japanese pollen antigen)-stimulated human CD4-positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG-DNA-treated B cells reduced Cry j 1-induced interleukin (IL)-5 and IL-13 production in CD4-positive cells. When the binding of PD-1 to PD-L1 was inhibited by PD-1-immunoglobulin (Ig), this chimera molecule reversed the previously described reductions in IL-5 and IL-13 production. In contrast, the CpG B-treated B cells increased both interferon (IFN)-γ and IL-12 production in the presence of Cry j 1-stimulated CD4-positive cells. CpG-DNA simultaneously reduced the expression of B7RP-1 [also known as inducible co-stimulator ligand (ICOSL), B7-H2] and the ligand of CD30 (CD30L). These results indicate that CpG-DNA induces co-inhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of co-stimulatory molecule ligands that can promote Th2 inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Antigens, Plant / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • B7-H1 Antigen / immunology*
  • Cell Communication / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Cytokines / immunology
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand / immunology
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Interleukin-13 / immunology
  • Interleukin-5 / immunology
  • Lymphocyte Activation / immunology
  • NF-kappa B p50 Subunit / immunology
  • Oligodeoxyribonucleotides / immunology*
  • Oligodeoxyribonucleotides / pharmacology
  • Plant Proteins / immunology
  • Pollen / immunology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Rhinitis, Allergic, Seasonal / immunology
  • Th2 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Antigens, Plant
  • B7-H1 Antigen
  • CD274 protein, human
  • CPG-oligonucleotide
  • Cry j I protein, Cryptomeria japonica
  • Cytokines
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Interleukin-13
  • Interleukin-5
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Oligodeoxyribonucleotides
  • PDCD1 protein, human
  • Plant Proteins
  • Programmed Cell Death 1 Receptor
  • Interleukin-12
  • Interferon-gamma