beta7 Integrin expression is not required for the localization of T cells to the intestine and colitis pathogenesis.
beta7 Integrins have been shown to have an important role in the localization of T cells to the intestine. Utilizing two different experimental mouse models of inflammatory bowel disease (IBD), this study was undertaken to determine if beta7 integrin expression is critical for T cell localization to the intestine and colitis pathogenesis. Transfer of CD4+ CD45RBhigh cells into immunodeficient mice results in colitis. To examine the role of beta7 integrins, donor cells were obtained from beta7 integrin gene-deficient animals and disease induction was examined following transfer into severe combined immunodeficiency (SCID) mice. Additionally, beta7 integrin gene-deficient animals were crossed to IL-2-deficient mice and the onset of spontaneous colitis that normally occurs in IL-2-deficient animals was examined. No differences in the onset or severity of spontaneous colitis was noted in animals that were deficient in both beta7 integrin and IL-2. In contrast, the onset of colitis in recipients of T cells from beta7 integrin-deficient donors was delayed significantly. In mice receiving beta7 integrin negative cells, the initial lack of colitis appeared to correlate with fewer numbers of CD3+beta7 integrin -/- donor lymphocytes present in the host colon. The eventual development of disease, however, was associated with increased numbers of donor beta7 integrin -/- lymphocytes. These results show that beta7 integrin expression is not absolutely required for T cell localization to the intestine and colitis pathogenesis.
Sydora
B C
BC
Division of Digestive Diseases, UCLA School of Medicine, USA. bsydora@ualberta.ca
Wagner
N
N
Lohler
J
J
Yakoub
G
G
Kronenberg
M
M
Muller
W
W
Aranda
R
R
D019264:Adoptive Transfer; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003092:Colitis / Q000235:genetics / Q000276:immunology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000503:physiopathology; D039641:Integrin beta Chains; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D016201:Receptors, Lymphocyte Homing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000473:pathology* / Q000637:transplantation
D039641:Integrin beta Chains; D016023:Integrins; D007376:Interleukin-2; D016201:Receptors, Lymphocyte Homing; C091368:integrin beta7; D017493:Leukocyte Common Antigens