Cognate antigen directs CD8+ T cell migration to vascularized transplants

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 G...

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Bibliographic Details
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:	eng
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
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Summary:	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.
ISSN:	0021-9738 1558-8238