CD45RChighCD4+ intestinal mucosal lymphocytes infiltrating in the inflamed colonic mucosa of a novel rat colitis model induced by TNB immunization.
To clarify the role of CD4(+) intestinal mucosal lymphocytes in chronic intestinal inflammation, we developed a new rat colitis model by immunization with 2,4,6-trinitrobenzenesulfonic acid (TNB) in an emulsion with an adjuvant followed by transrectal administration of a low dose of TNB. Moreover, we assessed the therapeutic effect of anti-CD4 monoclonal antibody (mAb) on this model. In concert with the development ofserum anti-TNB Abs, transmural and segmental colitis that mimics some characteristics of human Crohn's disease was induced in the immunized rats. Immunohistochemical analysis showed the increase of infiltrating lamina propria CD4(+) T cells. Flow-cytometric analysis of isolated cells from inflamed mucosa revealed that CD45RChighCD4(+) T cells were significantly increased. Interestingly, intraperitoneal administration of anti-CD4 mAbs could suppress severe inflammation in the model with decrease of anti-TNB Ab titer. After the treatment with anti-CD4 mAbs, CD45RChighCD4(+) T cells in the lamina propria and interferon-gamma mRNA expression in the colonic lamina propria CD4(+) T cells were decreased. These results indicated that Th1 CD4(+) intestinal mucosal T cells have a role in the progress of inflamed lesions in chronic enteritis. They implicate that a therapy targeting mucosal T cells expressing CD4 may be feasible in the treatment of human Crohn's disease.
School of Medicine, Keio University, Tokyo, Japan.
M
M
Watanabe
Y
Y
Hosoda
S
S
Okamoto
M
M
Yamazaki
N
N
Inoue
Y
Y
Ueno
Y
Y
Iwao
H
H
Ishii
N
N
Watanabe
Y
Y
Hamada
T
T
Yamada
T
T
Suzuki
T
T
Hibi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003092:Colitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000628:therapy; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007114:Immunization; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D017931:DNA Primers; D012333:RNA, Messenger; D014302:Trinitrobenzenesulfonic Acid; D017493:Leukocyte Common Antigens