The mechanism(s) of tolerance induction in T and B cells will be studied in detail in isolated cell populations, and in model systems in which essentially all cells interact with a specific "tolerogen". In the former case, T and B cells from tolerogen injected animals will be purified by affinity chromatography, for example, in which specific antibody to the tolerogen is attached to columns and cells bearing tolerogen are removed and analyzed. Interaction of lymphocytes with inhibitory doses of Concanavalin A and other lectins will be used in the second model. Both systems will be follwed in kinetic studies to determine the early membrane events in tolerance induction to an antigen or a lectin. The manipulation of tolerance in vivo and in vitro will also be studied in adoptive transfer systems in which the recipients are challenged with hapten-carrier protein conjugates. Unresponsiveness in T cells will then be evaluated in terms of carrier function, and B cell tolerance measured by the effect on hapten-specific plaque forming cell precursors. The involvement and role of "suppressor cells" in tolerance and the control of autoimmunity will be evaluated. Finally we will use these systems to study the nature of T vs B cell receptors. These studies should aid in our understanding of the immune response and in our ability to activate and "turn off" immunocompetent cells in various disease states.
NIH ExPorter
NIH ExPorter