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.

journal_name

Hum Immunol

journal_title

Human immunology

authors

Jugdé F,Boissier C,Birebent B,Vu N,D'halluin PN,Rioux-Leclercq N,Bretagne JF,Semana G,Heresebach D

doi

10.1016/j.humimm.2003.12.013

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

218-30

issue

3

eissn

0198-8859

issn

1879-1166

pii

S0198885904000102

journal_volume

65

pub_type

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