The migration of effector or memory T cells to the graft is a critical event in the rejection of transplanted organs. The prevailing view is that the key steps involved in T cell migration — 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 demonstrated in vivo that cognate antigen was necessary for the firm adhesion and transendothelial migration of CD8+ effector T cells specific to graft antigens and that both steps occurred independent of Gαi signaling. Presentation of cognate antigen by either graft endothelial cells or bone marrow–derived APCs that extend into the capillary lumen was sufficient for T cell migration. The adhesion and transmigration of antigen-nonspecific (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 cells or bone marrow–derived APCs in the migration of T cells across endothelial barriers and have important implications for the prevention and treatment of graft rejection.
Jeffrey M. Walch, Qiang Zeng, Qi Li, Martin H. Oberbarnscheidt, Rosemary A. Hoffman, Amanda L. Williams, David M. Rothstein, Warren D. Shlomchik, Jiyun V. Kim, Geoffrey Camirand, Fadi G. Lakkis
Gαi-independent migration of memory and effector T cells to heart allografts.
PTx-treated and untreated T cells were cotransferred to heart allograft recipients 2 days after transplantation, except where indicated. (