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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 α4β7) 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 α4β7 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 α4β7 and CD154 (CD40 ligand) on T cells. Our results suggest an important role of the appendix in the pathogenesis of colitis. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]