MECHANISMS OF T CELL MIGRATION TO VASCULARIZED ORGAN TRANSPLANTS

A critical event in the rejection of transplanted organs is the migration of effector or memory T cells to the graft. The prevailing view is that the key steps involved in this process, integrin-mediated firm adhesion followed by transendothelial migration, are dependent on the activation of Gαi-coupled chemokine receptors on T cells. In contrast to this view, we demonstrate in vivo that cognate antigen is necessary for the firm adhesion and transendothelial migration of CD8+ effector T cells specific to graft antigens and that both steps occur independent of Gαi signaling. Presentation of cognate antigen by either graft endothelial cells or bone marrow derived antigen presenting cells that extend into the capillary lumen was sufficient for T cell migration. The adhesion and transmigration of antigen non-specific (bystander) effector T cells, on the other hand, remained dependent on Gαi but required the presence of antigen-specific effector T cells. These findings underscore the primary role of cognate antigen presented by either endothelial or bone marrow derived antigen-presenting cells in the migration of T cells across endothelial barriers and have important implications for the prevention and treatment of graft rejection