T cell-associated CD18 but not CD62L, ICAM-1, or PSGL-1 is required for the induction of chronic colitis

The induction and perpetuation of chronic colitis are thought to involve a complex set of adhesive interactions between T cells and endothelial cells located on the vasculature within secondary lymphoid tissue and the intestine. The objective of this study was to assess the roles of T cell-associated CD18, CD62L ( L- selectin), ICAM- 1, and P- selectin glycoprotein ligand- 1 ( PSGL- 1) in the induction of chronic colitis in mice. CD4(+) CD25(-) T cells derived from either wild-type ( WT), CD18-deficient [ CD18 knockout ( KO)], CD62L KO, ICAM- 1 KO, or PSGL- 1 KO mice were adoptively transferred into recombinase activating gene-1 ( RAG-1)-deficient mice ( RAG KO mice) to assess the potential of these T cells to induce chronic colitis. At 8 - 10 wk following T cell transfer, we observed moderate to severe colitis as assessed by increases in colon weight- to- length ratios and by blinded histopathological analysis. In contrast, we found that transfer of CD18 KO T cells into RAG KO recipients resulted in the significant attenuation of colonic inflammation in these mice. Furthermore, we observed fewer infiltrating CD4(+) T cells in the colonic lamina propria in the CD18 KO3RAG KO group compared with the WT -> RAG KO group. Finally, message levels of colonic TNF-alpha, IL-1 beta, and IFN-gamma were significantly reduced in CD18 KO3RAG KO mice compared with colitic control animals. We conclude that T cell-associated CD18, but not CD62L, ICAM-1, or PSGL-1, is required for the development of chronic colitis.