Reduced responsiveness of HLA-B27 transgenic rat cells to TGF-β and IL-10-mediated regulation of IFN-γ production
✍ Scribed by Bi-Feng Qian; Susan L. Tonkonogy; R. Balfour Sartor
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 382 KB
- Volume
- 14
- Category
- Article
- ISSN
- 1078-0998
No coin nor oath required. For personal study only.
✦ Synopsis
Background:
We have reported that commensal luminal bacterial components induce an active in vitro IFN-␥ response in mesenteric lymph node (MLN) and intestinal cells from specific pathogen-free (SPF) HLA-B27 transgenic (TG) rats with chronic colitis but not in cells from non-diseased SPF non-TG, germ-free (GF) non-TG or GF TG rats.
Methods:
The study examined IL-12 stimulation of MLN IFN-␥ responses to luminal bacteria and regulation of these responses by suppressive cytokines.
Results: Exogenous IL-12 significantly increased the bacterial lysate-induced IFN-␥ response in SPF TG MLN cells, while bacterial lysate and IL-12 synergistically induced IFN-␥ from low baseline levels in cells obtained from both SPF and GF non-TG rats, and in GF TG cells. TGF- fully counteracted the effects of IL-12 and bacterial lysate on non-TG cells by almost completely inhibiting IFN-␥ production. In contrast, TG cells were less responsive to TGF--mediated downregulation with a substantial residual IFN-␥ response to IL-12 plus bacterial lysate. Further experiments showed that CD4 ϩ /CD25 ϩ cells had no inhibitory effect on the IFN-␥ production and were not required for TGF--mediated suppression. Addition of exogenous IL-10 also partially inhibited IFN-␥ production by non-TG cells but did not affect TG cells. Conversely, exogenous IL-12 preferentially suppressed bacterial lysate-induced TGF- and IL-10 production in TG rat cells.
Conclusions: An attenuated response to regulatory signals leads to uncontrolled potentiated induction of effector IFN-␥ responses to commensal bacteria in HLA-B27 TG rats that spontaneously develop chronic intestinal inflammation.