CD4(+) T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated with nonpathogenic Bacteroides vulgatus.
BACKGROUND
HLA-B27/beta2 microglobulin transgenic (TG) rats develop spontaneous colitis when raised under specific pathogen-free (SPF) conditions or after mono-association 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-1beta 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.
Hoentjen
Frank
F
Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA.
Tonkonogy
Susan L
SL
Qian
Bi-Feng
BF
Liu
Bo
B
Dieleman
Levinus A
LA
Sartor
R Balfour
RB
D000818:Animals; D001439:Bacteroides; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D003092:Colitis / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D030781:Organisms, Genetically Modified; D051381:Rats; D011923:Rats, Nude
D015796:HLA-B27 Antigen; D016753:Interleukin-10; D007371:Interferon-gamma