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.
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.
Department of Otorhinolaryngology, University of Fukui, Japan.
S
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Kubo
T
T
Yamada
Y
Y
Osawa
Y
Y
Ito
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N
Narita
S
S
Fujieda
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D052179:Antigens, Plant / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D052002:NF-kappa B p50 Subunit / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D052179:Antigens, Plant; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C408982:CPG-oligonucleotide; C065290:Cry j I protein, Cryptomeria japonica; D016207:Cytokines; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D018793:Interleukin-13; D015848:Interleukin-5; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009838:Oligodeoxyribonucleotides; C105992:PDCD1 protein, human; D010940:Plant Proteins; D061026:Programmed Cell Death 1 Receptor; D018664:Interleukin-12; D007371:Interferon-gamma