Basic ScienceAntibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn's disease in mice☆,☆☆
Section snippets
Adoptive transfer
Mesenteric lymph nodes were obtained from anesthetized SAMP-1/Yit mice (30–50 weeks old, maintained in a colony at the University of Virginia) and lymphocytes were rendered into a single-cell suspension as described by Kosiewicz25 and positively selected for CD4+ by magnetic beads (Miltenyi Biotech, CA). CD4+ lymphocytes were obtained, counted, and injected at 1×106 CD4+ lymphocytes per mouse intraperitoneally (IP) into 6–8 week old C3HeJ-SCID mice (Jackson Laboratories, Bar Harbor, ME). The
Expression of vascular immunoglobulin adhesion molecules
Immunostaining revealed increased staining for ICAM-1 in the mice adoptively transferred with CD4+ T cells from SAMP-1/Yit mice compared with SCID receiving CD4+ T cells from AKR mice (Figure 1).This staining was
Discussion
In a novel murine model of human Crohn's disease, we show that adoptive transfer of unfractionated CD4+ T cells from SAMP-1/Yit mice into SCID recipients induces expression of the endothelial adhesion molecules ICAM-1 and VCAM-1. Blocking both ICAM-1 and VCAM-1, but not either one alone, almost completely resolves the acute inflammatory infiltrate. Previous experiments in this25 and other46 models have shown that disease-causing T cells are of a Th1-like phenotype, producing interferon-γ
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Address requests for reprints to: R. Cartland Burns, M.D., Assistant Professor, University of Virginia Health Systems, Departments of Surgery and Pediatrics, P.O. Box 800709, Charlottesville, Virginia 22906. e-mail: [email protected]; fax: (804) 924-2656.
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Supported by the National Institutes of Health PO1 DK57880-01, grants DK55812 and DK70555.