Zusammenfassung
Background: Clinical and experimental studies suggest that appendectomy can protect against development of ulcerative colitis and Crohn's disease. However, how T cells in the appendix affect the development of colitis has not been clarified. Aim: To investigate the in vivo migration and activation of colitis- inducing CD62L(+) cells during development of chronic colitis. Methods: CD62L(+) CD4(+) ...
Zusammenfassung
Background: Clinical and experimental studies suggest that appendectomy can protect against development of ulcerative colitis and Crohn's disease. However, how T cells in the appendix affect the development of colitis has not been clarified. Aim: To investigate the in vivo migration and activation of colitis- inducing CD62L(+) cells during development of chronic colitis. Methods: CD62L(+) CD4(+) cells were fluorescently labeled and transferred to severe combined immunodeficient ( SCID) mice to induce colitis. In vivo migration of T cells into the mucosa of the appendix and colon was quantified by in vivo microscopy after 7 weeks. In a second experiment, unlabeled CD62L(+) CD4(+) cells were transferred, reisolated after 7 weeks, and adhesion molecule ( integrin alpha(4)beta(7)) and costimulatory molecule ( CD154) expression was analyzed. Results: Six to eight weeks after CD62L(+) CD4(+) cell transfer, SCID mice developed chronic colitis. In vivo microscopic analysis demonstrated a preferential migration of fluorescence- labeled CD62L(+) CD4(+) cells into the mucosa of the appendix versus the colon. Re- isolation of lamina propria cells from mice with colitis confirmed that CD62L(+) CD4(+) cell migration was significantly enhanced in the appendix, compared to the colon ( 3.5- fold). Furthermore, a higher proportion of CD62L(+) CD4(+) cells re- isolated from the appendix expressed integrin alpha(4)beta(7) and CD154 than from the colon. Conclusion: This study demonstrates the preferential migration of CD62L(+) CD4(+) cells into the appendix as compared to the colon. This migration pattern correlated with upregulation of integrin alpha(4)beta(7) and CD154 ( CD40 ligand) on T cells. Our results suggest an important role of the appendix in the pathogenesis of colitis. Copyright (C) 2005 S. Karger AG, Basel.
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