CD4+ T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus

Background: HLA-B27/beta 2 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-gamma mRNA, cecal myeloperoxidase, and cecal IL-1 beta 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-gamma 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.