title: Stimulation of peripheral blood and intestinal mucosa cells by synthetic CpG oligodeoxynucleotides.
abstract: The breakdown of tolerance to autologous bacterial flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic inflammation in inflammatory bowel diseases (IBD). To test whether bacterial DNA is at the origin of inflammation in IBD, we have examined the response of lamina propria (LPMC) or peripheral mononuclear cells (PBMC) and purified T cells from IBD patients and control patients to stimulations with a set of oligodeoxynucleotides (ODNs) characterized by the presence or absence of cytosine-guanosine dinucleotides (CpG) and/or 3' poly-guanosine (poly-G) extension. Furthermore we have evaluated the costimulatory activities of these ODNs on T cells activated via CD2 or CD3 pathway. We demonstrated that CpG ODNs induce higher proliferation of LPMC from inflammatory intestinal mucosa compared to healthy mucosa. We confirmed that CpG ODNs do not directly costimulate peripheral blood T cells activated by CD3 pathway. Finally, we revealed that CpG or non-CpG ODNs with 3' poly-G extension inhibit completely CD2 activation of purified PB or LP T-cells whereas only CpG ODNs without poly-G extension enhance proliferation and IFN-gamma production of PB T cells stimulated by CD2 pathway only in presence of NK and NK T cells. Our data suggest that NK T cells may be the primary target of ODNs and play a crucial role in indirect T-cell activation by ODN.
authors.affiliation: Laboratoire Universitaire d'Immunologie, Université de Rennes, Rennes, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jugdé
authors.forename: Christine
authors.initials: C
authors.lastname: Boissier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Birebent
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vu
authors.forename: Pierre-Nicolas
authors.initials: PN
authors.lastname: D'halluin
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bretagne
authors.forename: Gilbert
authors.initials: G
authors.lastname: Semana
authors.forename: Denis
authors.initials: D
authors.lastname: Heresebach
mesh_terms: D018801:CD2 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018899:CpG Islands / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D011068:Poly G / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018801:CD2 Antigens; D017252:CD3 Complex; D009838:Oligodeoxyribonucleotides; D011068:Poly G; D007371:Interferon-gamma