Cognate antigen directs CD8^sup +^ T cell migration to vascularized transplants

• Published in: The Journal of clinical investigation 2013-06, Vol.123 (6), p.2663
• Main Authors: Walch, Jeffrey M, Zeng, Qiang, Li, Qi, Oberbarnscheidt, Martin H, Hoffman, Rosemary A, Williams, Amanda L, Rothstein, David M, Shlomchik, Warren D, Kim, Jiyun V, Camirand, Geoffrey, Lakkis, Fadi G
• Format: Article
• Language: English
• Subjects: Biomedical research; Cell adhesion & migration; Chemokines; Colleges & universities; Endothelium; Heart; Lymphocytes; Proteins; Transplants & implants
• ISSN: 0021-9738; 1558-8238

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 Gα^sub i^-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^sup +^ effector T cells specific to graft antigens and that both steps occurred independent of Gα^sub i^ 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 Gα^sub i^, 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. [PUBLICATION ABSTRACT]