SUMMARYGerm-free HLA-B27 transgenic (TG) rats do not develop colitis, but colonization with specific pathogen-free (SPF) bacteria induces colitis accompanied by immune activation. To study host-dependent immune responses to commensal caecal bacteria we investigated cytokine profiles in mesenteric lymph node (MLN) cells from HLA-B27 TG versus nontransgenic (non-TG) littermates after in vitro stimulation with caecal bacterial lysates (CBL). Supernatants from CBL-stimulated unseparated T-or B-celldepleted MLN cells from HLA-B27 TG and non-TG littermates were analysed for IFN-g , IL-12, TNF, IL-10 and TGF-b production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN-g , IL-12 and TNF than did non-TG MLN cells . In contrast, CBL-stimulated non-TG MLN cells produced more IL-10 and TGF-b . T cell depletion abolished IFN-g and decreased IL-12 production, but did not affect IL-10 and TGF-b production. Conversely, neither IL-10 nor TGF-b was produced in cultures of B cell-depleted MLN. In addition, CD4 + T cells enriched from MLN of HLA-B27 TG but not from non-TG rats produced IFN-g when cocultured with CBL-pulsed antigen presenting cells from non-TG rats. Interestingly, IL-10 and TGF-b , but not IFN-g , IL-12 and TNF were produced by MLN cells from germ-free TG rats. These results indicate that the colitis that develops in SPF HLA-B27 TG rats is accompanied by activation of IFN-g -producing CD4+ T cells that respond to commensal bacteria. However, B cell cytokine production in response to components of commensal intestinal microorganisms occurs in the absence of intestinal inflammation.
HLA-B27 TG rats have an aberrant cell composition, altered functional TLR expression, and an intrinsic defect in IL-10 production in response to TLR ligands, which may result in exaggerated proinflammatory responses to commensal enteric bacteria and uncontrolled inflammation in this colitis model.
An attenuated response to regulatory signals leads to uncontrolled potentiated induction of effector IFN-gamma responses to commensal bacteria in HLA-B27 TG rats that spontaneously develop chronic intestinal inflammation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.