REGULATORY T AND B CELL CIRCUITS IN TRANSPLANTATION

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We plan to utilize mouse monoclonal antibodies in experimental canine in vitro and in vivo transplantation models. In 1 and 2 mixed lymphocyte (MLC), mixed lymphocyte islet (MLIC), and mixed lymphocyte kidney (MLKC) reactions we will measure the effects of monoclonals raised against canine T lymphocyte subsets and B cell Ia antigens. We will also test monoclonals raised against idiotypic determinants of primed T cells (anti-specific receptor sites for major histocompatibility complex disparities and for tissue specific differentiation antigens on pancreatic islet and kidney cells). In so doing we will study the in vitro activity of cells derived from rejecting kidneys and free draining pancreatic vascularized segments transplanted simultaneously with respect to anti-tissue specific vs. alloimmune reactivity. Several strategies in raising anti-idiotypic monoclonals are delineated, as well as in vivo experiments in which they will be used (compared with anti-T cell subset and anti-Ia reagents) to test effects on pancreatic and kidney transplantation. Because of the repeated rapid development of immune elimination, putatively anti-idiotypic immunity, we have designed experiments to induce an unresponsive state. Transplantation of organs perfused with monoclonals against canine Ia antigens are described as well as a plan to inactivate pancreatic acinar secretion in transplants using an anti-acinar cell reagent.