Cognate antigen directs CD8+ T cell migration to vascularized transplants

J Clin Invest. 2013 Jun;123(6):2663-71. doi: 10.1172/JCI66722. Epub 2013 May 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • GTP-Binding Protein alpha Subunits, Gi-Go / physiology
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • 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*


  • Receptors, Chemokine
  • GTP-Binding Protein alpha Subunits, Gi-Go