BACKGROUND: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. METHODS: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. RESULTS: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. CONCLUSIONS: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.
BACKGROUND: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. METHODS: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. RESULTS: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. CONCLUSIONS: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.
Authors: M M Maurice; H Nakamura; E A van der Voort; A I van Vliet; F J Staal; P P Tak; F C Breedveld; C L Verweij Journal: J Immunol Date: 1997-02-01 Impact factor: 5.422
Authors: I J Fuss; M Neurath; M Boirivant; J S Klein; C de la Motte; S A Strong; C Fiocchi; W Strober Journal: J Immunol Date: 1996-08-01 Impact factor: 5.422
Authors: A Grabig; D Paclik; C Guzy; A Dankof; D C Baumgart; J Erckenbrecht; B Raupach; U Sonnenborn; J Eckert; R R Schumann; B Wiedenmann; A U Dignass; A Sturm Journal: Infect Immun Date: 2006-07 Impact factor: 3.441
Authors: Silvio Danese; Miquel Sans; David M Spencer; Ivy Beck; Fernando Doñate; Marian L Plunkett; Carol de la Motte; Raymond Redline; David E Shaw; Alan D Levine; Andrew P Mazar; Claudio Fiocchi Journal: Gut Date: 2006-12-14 Impact factor: 23.059
Authors: Heitor S P de Souza; Gail A West; Nancy Rebert; Carol de la Motte; Judy Drazba; Claudio Fiocchi Journal: Gastroenterology Date: 2012-06-26 Impact factor: 22.682