Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+T cells

The objectives of this study were to quantify colonic cytokine and endothel ial cell adhesion molecule (ECAM) expression in the colons of severe combin ed immunodeficient (SCID) mice reconstituted with different subsets of CD4 T lymphocytes. We found that animals injected with CD45RB(high) but not CD 45RB(low) T cells or phosphate-buffered saline (PBS) developed clinical evi dence of colitis at 6-8 weeks following reconstitution, as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopath ology. Concurrent with the onset of distal bowel inflammation was enhanced expression of a variety of Th1 and macrophage-derived cytokines including i nterferon gamma, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6 , IL-12, and IL-18 lymphotoxin-beta. In addition, message levels and vascul ar surface expression of ICAM-1, VCAM-1, and MAdCAM-1 were all significantl y enhanced in the colitic SCID mice reconstituted with CD45RB(high) T cells compared with SCID mice reconstituted with PBS or CD45RB(low) T cells that did not develop disease. Significant increases in some of these ECAMs were also noted in the cecum and stomach and to a lesser degree in the small bo wel. Our data confirm that reconstitution of SCID mice with CD45RB(high) bu t not CD45RB(low) T cells induces chronic colitis, and that the colonic inf lammation is associated with enhanced expression of proinflammatory cytokin es and different ECAMs in the colon. Furthermore, our studies demonstrate t hat reconstitution of SCID mice with CD45RB(high) T cells enhances ECAM exp ression in tissues distant from the site of active inflammation.