Intraepithelial lymphocytes coinduce nitric oxide synthase in intestinal epithelial cells

The study of mucosal immunity has revealed that complex reciprocal interact ions occur between intestinal intraepithelial lymphocytes (IEL) and intesti nal epithelial cells (IEC). The present study focuses on the induction of i nducible nitric oxide (NO) synthase in cocultures of freshly isolated rat I EL and the rat epithelial cell line IEC-18 after the addition of interleuki n-1 beta (IL-1 beta), tumor necrosis factor-alpha, or lipopolysaccharide. W hen IEL and IEC were separated using Transwell chambers, NO synthesis was n ot induced, indicating that cell-cell contact was required. Culture of IEC- 18 with IEL, even in the absence of inflammatory stimuli such as IL-1 beta, resulted in upregulation of class I and II antigens on IEC-18, due to the interferon-gamma (IFN-gamma) that is constitutively produced by IEL. Additi on of anti-IFN-gamma antibody to the NO-producing cocultures resulted in in hibition of NO synthesis as well as the upregulation of class I and II anti gen expression. These data indicate that IFN-gamma production by IEL condit ions IEC for the expression of other components of the inflammatory process .