Hyperexpression of inducible costimulator on lamina propria mononuclear cells in rat dextran sulfate sodium colitis.
OBJECTIVE
The authors have previously shown that a third member of the CD28 family, inducible costimulator (ICOS), was increased in the inflamed intestinal mucosa of murine experimental colitis, and that the blockade of ICOS ameliorated the development of colitis. However, the role of ICOS in rat intestinal inflammation and its expression profile remains unclear. In the present study, the authors investigated the involvement of ICOS in the development of rat dextran sulfate sodium (DSS)-induced colitis, and the therapeutic potential of anti-ICOS monoclonal antibody (mAb) in colitis.


METHODS
The authors first examined expression of ICOS protein in normal rat by immunohistochemistry and flow cytometry. Sprague-Dawley rats were fed 3.0% DSS. The expression of ICOS on infiltrating lamina propria mononuclear cells and splenocytes were examined. The DSS-fed rats were then administered anti-ICOS mAb to test its effect on the development of colitis.


RESULTS
Unlike mice and human, ICOS was expressed on a part of CD4+ T-cells from the thymus, spleen, mesenteric lymph nodes and lamina propria. Levels of ICOS on CD4+ T-cells from the spleen and colonic lamina propria were significantly upregulated after Concanavalin A (Con A) stimulation. In addition, ICOS was also upregulated on CD4+ T-cells from DSS-fed rats compared with those from non DSS-fed rats. However, anti-ICOS mAb did not ameliorate the development of both acute and chronic DSS colitis.


CONCLUSIONS
These results suggest that the different expression of ICOS in rats plays a distinct role in rat intestinal inflammation.
Ishii
Kenichi
K
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Kanai
Takanori
T
Totsuka
Teruji
T
Uraushihara
Koji
K
Ishikura
Takahiro
T
Yamazaki
Motomi
M
Okamoto
Ryoici
R
Araki
Akihiro
A
Miyata
Tatsuya
T
Tezuka
Katsuaki
K
Nakamura
Tetsuya
T
Watanabe
Mamoru
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate; D005434:Flow Cytometry; D007150:Immunohistochemistry; D060889:Inducible T-Cell Co-Stimulator Protein; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; C556694:Icos protein, mouse; C556695:Icos protein, rat; D060889:Inducible T-Cell Co-Stimulator Protein; D016264:Dextran Sulfate