Expression of B7 costimulatory molecules by cells infiltrating the colon in experimental colitis induced by oral dextran sulfate sodium in the mouse.
OBJECTIVE
T-cell activation, mediated by the interaction with major histocompatibility complex (MHC)-peptide complexes and B7 costimulatory molecules on antigen-presenting cells, is an essential event in the pathogenesis of inflammatory bowel disease (IBD). We investigated the expression of B7 costimulatory molecules on cells in the colon in an experimental mouse model of IBD to determine whether the B7/ligand interaction could provide a target for therapeutic intervention in IBD.


METHODS
Experimental colitis was induced in mice by oral consumption of water substituted with 5% dextran sulfate sodium (DSS). Mice (n=4) were killed 1, 2, 3, 4 and 7 days after commencing DSS consumption, and colonic tissue was collected and examined immunohistochemically for T cells, B cells, macrophages and cells expressing B7-1 or B7-2.


RESULTS
Compared to control mice drinking water, macrophage numbers in the colonic epithelium were elevated sevenfold by day 1 and T cells were elevated threefold by day 3 following commencement of DSS consumption. Numbers of infiltrating B7-positive (B7+) cells were not significantly elevated until day 7 when B7-1+, B7-2+ cells and macrophages were increased 20-fold compared to normal mice.


CONCLUSIONS
These results demonstrate that an initial and rapid infiltration of the colonic epithelium by B7-negative macrophages is followed by an infiltration of T cells and subsequent upregulation of the B7 costimulatory molecules potentiating the inflammatory reaction in this disease model. These results suggest an intervention strategy based on the blockade of the B7-costimulatory axis could find application in the treatment of inflammatory bowel disease.
Grose
R H
RH
Cooperative Research Centre for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, South Australia.
Howarth
G S
GS
Xian
C J
CJ
Hohmann
A W
AW
D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000166:cytology* / Q000378:metabolism*; D016264:Dextran Sulfate / Q000008:administration & dosage; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D016264:Dextran Sulfate