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Cognate antigen directs CD8+ T cell migration to vascularized transplants.
|Title||Cognate antigen directs CD8+ T cell migration to vascularized transplants.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Walch JM, Zeng Q, Li Q, Oberbarnscheidt MH, Hoffman RA, Williams AL, Rothstein DM, Shlomchik WD, Kim JV, Camirand G, Lakkis FG|
|Journal||The Journal of clinical investigation|
|Date Published||2013 Jun 3|
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.
|Alternate Journal||J. Clin. Invest.|