In our laboratory, previous studies of the cytotoxicity of lymphocytes from the peripheral blood of patients with Inflammatory Bowel Disease (IBD) for colonic epithelial cells have shown that the killer cells are non-phagocytic and lack both immunoglobulin determinants. However, the cytotoxic cells possess surface receptors capable of binding to the Fc fragment of aggregated human immunoglobulin. In addition, some of our other studies suggest either that cytophilic immunoglobulin or antigen-antibody complexes may be involved in the mechanism of cytotoxicity. The experiments outlined in this proposal are based on preliminary observations that IBD lymphocytes, when incubated for 4 days at 37 degrees C, release a factor(s) into the medium which will convey specific cytotoxicity for colonic epithelial cells to lymphocytes from healthy volunteers. We intend to characterize the active factor(s) and the experiments described represent the first steps to achieve this aim. They are directed first at detecting the presence of an immunoglobulin in the supernatants of the incubated lymphocytes, either as Ig or as antigen-antibody complexes, which conveys specific cytotoxicity for colonic cells to normal lymphocytes. Subsequent techniques for identification of the factor(s) will depend on the results of these preliminary experiments. It is hoped that the results of these and previous studies will elucidate further the mechanisms of the cytotoxicity and, in turn, will give important leads to the future understanding of the etiopathogenesis and improved treatment of IBD.
NIH ExPorter
NIH ExPorter