Cognate antigen directs CD8+ T cell migration to vascularized transplants

• Published in: The Journal of clinical investigation 2013-06, Vol.123 (6), p.2663-2671
• 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: Adoptive Transfer; Animals; Antigen Presentation; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - transplantation; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - physiology; CD8-Positive T-Lymphocytes - transplantation; Cell Adhesion; Coronary Vessels - immunology; Coronary Vessels - pathology; Endothelial Cells - immunology; Endothelial Cells - metabolism; Graft Rejection - immunology; Graft Rejection - prevention & control; GTP-Binding Protein alpha Subunits, Gi-Go - physiology; Heart Transplantation - immunology; Immunotherapy, Adoptive; Kidney - blood supply; Kidney - immunology; Kidney Transplantation - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microscopy, Fluorescence; Myocardium - immunology; Receptors, Chemokine - physiology; Signal Transduction; Time-Lapse Imaging; Transendothelial and Transepithelial Migration - immunology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI66722

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.