title: Cognate antigen directs CD8+ T cell migration to vascularized transplants.
abstract: 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.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Walch
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zeng
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Martin H
authors.initials: MH
authors.lastname: Oberbarnscheidt
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Hoffman
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Williams
authors.forename: David M
authors.initials: DM
authors.lastname: Rothstein
authors.forename: Warren D
authors.initials: WD
authors.lastname: Shlomchik
authors.forename: Jiyun V
authors.initials: JV
authors.lastname: Kim
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Camirand
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology* / Q000637:transplantation; D002448:Cell Adhesion; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D007668:Kidney / Q000098:blood supply / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000276:immunology; D019707:Receptors, Chemokine / Q000502:physiology; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*
chemical_list: D019707:Receptors, Chemokine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go