Divergent cell cycle kinetics underlie the distinct functional capacity of mucosal T cells in Crohn's disease and ulcerative colitis

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Abstract
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.