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

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2007-06, Vol.292 (6), p.G1706-G1714
• Main Authors: Ostanin, Dmitry V, Furr, Kathryn L, Pavlick, Kevin P, Gray, Laura, Kevil, Christopher G, Shukla, Deepti, D'Souza, Dwain, Hoffman, Jason M, Grisham, Matthew B
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Biochemistry; CD18 Antigens - genetics; CD18 Antigens - immunology; CD18 Antigens - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; Cell adhesion & migration; Cell Proliferation; Cells, Cultured; Chronic Disease; Colitis - immunology; Colitis - metabolism; Colitis - pathology; Colon - immunology; Colon - metabolism; Colon - pathology; Disease Models, Animal; Glycoproteins; Homeodomain Proteins - genetics; Homeodomain Proteins - immunology; Homeodomain Proteins - metabolism; Inflammatory bowel disease; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - immunology; Intercellular Adhesion Molecule-1 - metabolism; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-2 Receptor alpha Subunit - analysis; L-Selectin - genetics; L-Selectin - immunology; L-Selectin - metabolism; Lymphocyte Activation; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Pathology; Peptide Fragments - genetics; Peptide Fragments - metabolism; RNA, Messenger - metabolism; Rodents; Severity of Illness Index; T cell receptors; Time Factors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00573.2006

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 KO-->RAG KO group compared with the WT-->RAG KO group. Finally, message levels of colonic TNF-alpha, IL-1beta, and IFN-gamma were significantly reduced in CD18 KO-->RAG 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.