title: Preferential migration of CD62L cells into the appendix in mice with experimental chronic colitis.
abstract: 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.
  
  
  OBJECTIVE
  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 alpha4beta7) 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 alpha4beta7 and CD154 than from the colon.
  
  
  CONCLUSIONS
  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 alpha4beta7 and CD154 (CD40 ligand) on T cells. Our results suggest an important role of the appendix in the pathogenesis of colitis.
authors.affiliation: Department of Surgery, University of Regensburg, Regensburg, Germany. stefan.farkas@klinik.uni-regensburg.de
authors.forename: S A
authors.initials: SA
authors.lastname: Farkas
authors.forename: M
authors.initials: M
authors.lastname: Hornung
authors.forename: Christine
authors.initials: C
authors.lastname: Sattler
authors.forename: M
authors.initials: M
authors.lastname: Steinbauer
authors.forename: M
authors.initials: M
authors.lastname: Anthuber
authors.forename: F
authors.initials: F
authors.lastname: Obermeier
authors.forename: H
authors.initials: H
authors.lastname: Herfarth
authors.forename: H J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: E K
authors.initials: EK
authors.lastname: Geissler
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001062:Appendectomy; D001065:Appendix / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D003106:Colon / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D016023:Integrins / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D015430:Weight Gain
chemical_list: D016023:Integrins; C071777:integrin alpha4beta7; D019041:L-Selectin; D023201:CD40 Ligand