Preferential migration of CD62L cells into the appendix in mice with experimental chronic colitis.
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.
Farkas
S A
SA
Department of Surgery, University of Regensburg, Regensburg, Germany. stefan.farkas@klinik.uni-regensburg.de
Hornung
M
M
Sattler
Christine
C
Steinbauer
M
M
Anthuber
M
M
Obermeier
F
F
Herfarth
H
H
Schlitt
H J
HJ
Geissler
E K
EK
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
D016023:Integrins; C071777:integrin alpha4beta7; D019041:L-Selectin; D023201:CD40 Ligand