Reduced ratio of protective versus proinflammatory cytokine responses to commensal bacteria in HLA-B27 transgenic rats.
Germ-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- cell-depleted MLN cells from HLA-B27 TG and non-TG littermates were analysed for IFN-gamma, IL-12, TNF, IL-10 and TGF-beta production. Our results show that unfractionated TG MLN cells stimulated with CBL produced more IFN-gamma, IL-12 and TNF than did non-TG MLN cells. In contrast, CBL-stimulated non-TG MLN cells produced more IL-10 and TGF-beta. T cell depletion abolished IFN-gamma and decreased IL-12 production, but did not affect IL-10 and TGF-beta production. Conversely, neither IL-10 nor TGF-beta 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-gamma when cocultured with CBL-pulsed antigen presenting cells from non-TG rats. Interestingly, IL-10 and TGF-beta, but not IFN-gamma, 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-gamma-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.
Dieleman
L A
LA
Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Hoentjen
F
F
Qian
B-F
BF
Sprengers
D
D
Tjwa
E
E
Torres
M F
MF
Torrice
C D
CD
Sartor
R B
RB
Tonkonogy
S L
SL
D000818:Animals; D030801:Animals, Genetically Modified; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001419:Bacteria / Q000276:immunology*; D002432:Cecum / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D005856:Germ-Free Life; D015796:HLA-B27 Antigen / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D015796:HLA-B27 Antigen; D012333:RNA, Messenger