Obermeier, Florian and Strauch, U. G. and Dunger, N. and Grunwald, N. and Rath, H. C. and Herfarth, Hans and Schoelmerich, Juergen and Falk, Werner (2005) In vivo CpG DNA/toll-like receptor 9 interaction induces regulatory properties in CD4(+)CD62L(+) T cells which prevent intestinal inflammation in the SCID transfer model of colitis. GUT, 54 (10). pp. 1428-1436. ISSN 0017-5749,
Full text not available from this repository. (Request a copy)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 c, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; BACTERIAL-DNA; BOWEL-DISEASE; ENTERIC MICROFLORA; DENDRITIC CELLS; CROHNS-DISEASE; PLASMID DNA; MICE; OLIGONUCLEOTIDES; MOTIFS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Apr 2021 08:57 |
| Last Modified: | 26 Apr 2021 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35569 |
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