Differential susceptibility of heart, skin, and islet allografts to T cell-mediated rejection

Although it is widely accepted that there is a hierarchy in the susceptibil ity of different allografts to rejection, the mechanisms responsible are un known. We show that the increased susceptibility of H-2K(b+) skin and islet allografts to rejection is not based on their ability to activate more H-2 K(b)-specific T cells in vivo; heart allografts stimulate the activation an d proliferation of many more H-2K(b)-specific T cells than either skin or i slet allografts. Rejection of all three types of graft generate memory cell s by 25 days posttransplant. These data pro,ide evidence that neither tissu e-specific Ags nor, surprisingly, the number of APCs carried in the graft d ictate their susceptibility to T cell-mediated rejection and suggest that t he graft microenvironment and size may play a more important role in determ ining the susceptibility of an allograft to rejection and resistance to tol erance induction.