Levinus A. Dieleman and R. Balfour Sartor share senior authorship of this manuscript.
CD4+ T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus
Article first published online: 19 DEC 2006
Copyright © 2006 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 13, Issue 3, pages 317–324, March 2007
How to Cite
Hoentjen, F., Tonkonogy, S. L., Qian, B.-F., Liu, B., Dieleman, L. A. and Sartor, R. B. (2007), CD4+ T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus. Inflamm Bowel Dis, 13: 317–324. doi: 10.1002/ibd.20040
- Issue published online: 16 FEB 2007
- Article first published online: 19 DEC 2006
- Manuscript Accepted: 17 OCT 2006
- Manuscript Received: 7 JUN 2006
- U.S. Public Health Service. Grant Numbers: K08 DK02551, R01 DK40249, P30 DK34987
- AGIKO grant from The Netherlands Organization for Health Research and Development. Grant Number: 920-03-300
- Bacteroides vulgatus;
- transgenic rats
Background: HLA-B27/β2 microglobulin transgenic (TG) rats develop spontaneous colitis when raised under specific pathogen-free (SPF) conditions or after monoassociation with Bacteroides vulgatus (B. vulgatus), whereas germ-free TG rats fail to develop intestinal inflammation. SPF HLA-B27 TG rnu/rnu rats, which are congenitally athymic, remain disease free. These results indicate that commensal intestinal bacteria and T cells are both pivotal for the development of colitis in TG rats. However, it is not known if T cells are also required in the induction of colitis by a single bacterial strain. The aim of this study was therefore to investigate the role of T cells in the development of colitis in B. vulgatus–monoassociated HLA-B27 TG rats.
Methods: HLA-B27 TG rnu/rnu and rnu/+ rats were monoassociated with B. vulgatus for 8–12 weeks. CD4+ T cells from mesenteric lymph nodes (MLNs) of B. vulgatus–monoassociated rnu/+ TG donor rats were transferred into B. vulgatus–monoassociated rnu/rnu TG recipients.
Results:B. vulgatus–monoassociated rnu/+ rats showed higher histologic inflammatory scores and elevated colonic interferon-γ mRNA, cecal myeloperoxidase, and cecal IL-1β levels compared to those in rnu/rnu TG rats that did not contain T cells. After transfer of CD4+ cells from colitic B. vulgatus–monoassociated rnu/+ TG donor rats, B. vulgatus–monoassociated rnu/rnu TG recipients developed colitis that was accompanied by B. vulgatus-induced IFN-γ production by MLN cells in vitro and inflammatory parameters similar to rnu/+ TG rats.
Conclusions: These results implicate CD4+ T cells in the development of colitis in HLA-B27 TG rats monoassociated with the nonpathogenic bacterial strain B. vulgatus.
(Inflamm Bowel Dis 2007)