MODIFICATION OF LOCAL AND SYSTEMIC ALLOGRAFT REJECTION

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A number of different mechanisms exist to effect allograft rejection. The role of the lymphocyte is central in graft rejection; ample evidence exists that the helper T cell and the cytolytic T cell can effect graft loss. It is also clear that events occurring locally at the graft site are distinct from the systemic response to the allograft. The sponge matrix allograft model provides ready access to cells which accumulate at the site of allograft rejection. In combination with limiting dilution analysis which can identify small numbers of sensitized cells, we can readily assess events associated with local and systemic allograft immunity. Using these functional assessments of lymphocytes rather than radiolabel eliminates the need to introduce radiolabelled cells into the intravascular space. We plan to use these techniques to define these local and systemic events according to the tissue transplanted. Once these events are defined for various tissue we plan to use either local or systemic immunosuppression to modify them. The long term goal is to employ local immunosuppression to render the animal's systemic immune apparatus intact.