MECHANISMS OF INTESTINAL EPITHELIAL-CELL INJURY AND COLITIS IN INTERLEUKIN-2 (IL2)-DEFICIENT MICE

Epithelial cell (EC) injury is a feature of all inflammatory bowel dis orders (IBD). Although the mechanisms of EC injury are incompletely un derstood, it has been proposed that T-cell-mediated cytotoxicity and p roduction of inflammatory cytokines are involved. This hypothesis was tested using the interleukin 2-deficient (IL2(-/-)) mouse model of LED and cultures of primary colonic EC to determine if abnormal cytokine production or cytotoxicity by colonic T cells cause EC injury. Althoug h capable of cell-mediated killing of allogeneic target cells, IL2(-/- ) colonic T cells were unable to lyse syngeneic colonic EC. During dis ease progression, large numbers of IL4, TNF-alpha, and IFN-gamma-produ cing CD4(+) and CD8(+) cells accumulated within the intraepithelial sp aces and lamina propria of the colon of IL2(-/-) mice. Although coloni c EC expressed receptors for IFN-gamma and TNF-alpha, these cytokines did not adversely affect EC viability or growth in vitro consistent wi th these cytokines not being the primary mediators of EC injury in IBD . Our novel colonic EC culture system provides an in vitro accessible system in which to investigate further the nature of EC-lymphocyte int eractions. (C) 1998 Academic Press.