Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance.
We report here a murine model for experimental chronic colitis where administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol induced inflammation of large intestine in susceptible (C3H/HeJ and BALB/c) but not resistant (C57BL/6 and DBA/2) mouse strains. We queried whether mucosal trinitrophenyl (TNP)-specific B cell responses were induced in mice with TNBS-induced colitis, and if induction of tolerance to TNBS by oral administration of this hapten protected mice from development of colitis. Isotypes and subclasses of polyclonal and TNP-specific Ab-forming cells (AFC) were assessed in mucosal and peripheral lymphoid tissues of C3H/HeJ mice with TNBS-induced colitis. Increased numbers of IgA- and IgG-secreting cells were found in the inflamed colon lamina propria. Inflamed colonic tissue also contained high frequencies of IgG anti-TNP AFC (predominantly of IgG1, IgG2a, and IgG2b subclasses); however, anti-TNP responses in noninflamed mucosal tissues of mice with colitis exhibited dominant IgA and IgM with low IgG anti-TNP responses. CD4+ T cells stimulated with TNP-splenocytes produced more IFN-gamma and less IL-4, suggesting a Th1-type response. Oral administration of TNBS before induction of colitis markedly decreased mucosal anti-TNP responses and completely inhibited anti-TNP IgG2a and IgG2b responses. Control mice did not show inhibition of anti-TNP AFC responses or TNBS-induced colitis. Intracolonic sensitization of susceptible C3H/HeJ mice with TNBS induces a localized IgG anti-TNP B cell response in the inflamed tissue, whereas prior oral administration of TNBS results in unresponsiveness to this agent and protects mice from development of TNBS-induced colitis.
Elson
C O
CO
Department of Medicine, University of Alabama at Birmingham Medical Center 35294, USA.
Beagley
K W
KW
Sharmanov
A T
AT
Fujihashi
K
K
Kiyono
H
H
Tennyson
G S
GS
Cong
Y
Y
Black
C A
CA
Ridwan
B W
BW
McGhee
J R
JR
D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000633:toxicity; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D014301:Trinitrobenzenes / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000008:administration & dosage / Q000276:immunology
D016207:Cytokines; D000939:Epitopes; D006241:Haptens; D007166:Immunosuppressive Agents; D014301:Trinitrobenzenes; D014302:Trinitrobenzenesulfonic Acid