Article Text
Abstract
Background and methods: Cytosin-guanosin dinucleotide (CpG) motifs of bacterial DNA are known to be potent activators of innate immunity. We have shown previously that administration of CpG containing oligodeoxynucleotide (CpG-ODN) to mice before the onset of dextran sodium sulphate induced colitis ameliorated colitis and inhibited induction of proinflammatory cytokines. To investigate the possible involvement of CD4+ T cells in the prophylactic CpG-ODN effects, we used the SCID transfer model of colitis.
Results: CD4+CD62L+ T cells from CpG-ODN treated donors did not induce significant intestinal inflammation in SCID recipients, in contrast with control cells. Additionally, cotransfer of these cells with CD4+CD62L+ cells from normal mice protected recipient animals from colitis, indicating regulatory activity. Also, CD4+CD62L+ cells from toll-like receptor 9 deficient animals induced a significantly more severe colitis in SCID recipients than cells from wild-type littermate controls, suggesting a similar protective role of “endogenous” bacterial DNA leading to a less “aggressive” phenotype of these cells. There was no detectable difference in regulatory T cell surface markers between aggressive and attenuated cell pools but attenuated cell pools showed reduced proliferation in vitro and in vivo and produced less interferon γ, interleukin (IL)-5, and IL-6 after anti-CD3 stimulation.
Conclusions: Collectively, our data support the concept that both endogenous bacterial DNA and exogenously supplied CpG motifs of bacterial DNA induce regulatory properties in CD4+ T cells. Therefore, bacterial DNA derived from the normal gut flora may contribute essentially to the homeostasis between effector and regulatory immune mechanisms in healthy individuals to protect them from chronic intestinal inflammation.
- IBD, inflammatory bowel disease
- CpG, cytosin-guanosin dinucleotide
- CpG-ODN, CpG containing oligodeoxynucleotide
- TLR, toll-like receptor
- IL, interleukin
- TNF, tumour necrosis factor
- IFN-γ, interferon γ
- TGF-β, transforming growth factor β
- PBS, phosphate buffered saline
- RT-PCR, reverse transcription-polymerase chain reaction
- experimental colitis
- CpG motifs
- bacterial DNA
- SCID transfer model of colitis
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- IBD, inflammatory bowel disease
- CpG, cytosin-guanosin dinucleotide
- CpG-ODN, CpG containing oligodeoxynucleotide
- TLR, toll-like receptor
- IL, interleukin
- TNF, tumour necrosis factor
- IFN-γ, interferon γ
- TGF-β, transforming growth factor β
- PBS, phosphate buffered saline
- RT-PCR, reverse transcription-polymerase chain reaction
Footnotes
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↵* F Obermeier and UG Strauch contributed equally to this work.
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Conflict of interest: None declared.
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Published online first 5 May 2005