MAJORITY OF GLIADIN-SPECIFIC T-CELL CLONES FROM CELIAC SMALL-INTESTINAL MUCOSA PRODUCE INTERFERON-GAMMA AND INTERLEUKIN-4

An abnormal mucosal cell-mediated immune response plays a fundamental role in the pathogenesis of celiac disease. To characterize locally in filtrating T cells, gliadin-specific T-cell clones were isolated from two treated celiac patients. Mucosal biopsies were cultured in vitro f or 24 hr with a peptic-tryptic digest (PT) of-gliadin. T-cell clones ( TCC) were then isolated by limiting dilution. The production of interf eron-gamma (IFN-gamma) and interleukin-4 (IL-4) was evaluated by ELISA in culture supernatants obtained after a short incubation with anti-C D3 and PMA, or with antigen. Twenty-two TCC were specific for gliadin and/or PT. All were CD3(+), CD4(+), CD8(-), TCR alpha beta(+). Ln one such clone the PT-specific response was inhibited by an anti-DO, but n ot by an anti-DR antibody. Of the five gliadin-specific TCC examined, four produced IL-4 and high levels of IFN-gamma; the remaining one ini tially produced only IL-4, but subsequently also IFN-gamma. All clones obtained from the celiac mucosa, including the gliadin-specific ones, produced high levels of IFN-gamma, in most cases with IL-4. This cyto kine profile could explain most of the immunological features of the c eliac mucosa.