ORGAN TRANSPLANTS: ANALYSIS OF MIGRATING LYMPHOCYTES

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Many potential mechanisms of graft rejection exist. Study of these mechanisms must take into account migratory patterns of sensitized cells; in the animal the graft alloantigen may be far removed from lymphoid depots and a particular cell can only exert an effect if it can get to the graft. Investigators of lymphocyte trafficking have had uncertain results as to whether trafficking is a specific or nonspecific phenomenon. The problems with these previous studies however include: (a) An assumption that only activated cells are those rapidly dividing i.e. those which take up radioactive label. (b) The effect of the label on the ability of cells to migrate. (c) Injection of labeled cells into the vascular compartment when in fact they may not normally have access. These studies have shown that lymphocyte migration depends on (1) the subpopulation to which the lymphocyte belongs, (2) the state of activation of the lymphocyte, and (3) the host immune state. We propose to utilize the limiting dilution assay technique to study the distribution of sensitized proliferating and precytotoxic/cytotoxic cells throughout the sponge allograft sensitized mouse. Using these functional assessments of lymphocytes rather than radiolabel eliminates the need to introduce radiolabeled cells into the intravascular space. The use of the sponge allograft model in the mouse allows for easy access to all compartments including the cells infiltrating the allograft.