title: T-cell migration to vascularized organ allografts.
abstract: OBJECTIVE
  To review the classical paradigm of leukocyte migration and present new evidence that cognate antigen, and not signaling via Gαi-coupled chemokine receptors, drives the migration of effector and memory T cells into vascularized organ transplants.
  
  
  RESULTS
  Blocking Gαi function does not hinder integrin-dependent T-cell migration to heart and kidney allografts or significantly delay acute rejection. T-cell firm adhesion and transmigration is instead mediated by engagement of the T cell receptor for antigen (TCR) on antigen-specific (antidonor) T cells by cognate antigen presented by either graft endothelial cells or bone marrow-derived antigen-presenting cells that reach into the vascular lumen. Influx of bystander T cells is Gαi-dependent but occurs only if antigen-specific T cells are present.
  
  
  CONCLUSIONS
  Antigen-driven migration of effector and memory T cells sheds new light on the pathogenesis of transplant rejection and predicts that interrupting the TCR-triggered 'inside-out' signaling pathway, rather than that initiated by Gαi-coupled chemokine receptors, is a key approach to preventing rejection.
authors.affiliation: aThomas E. Starzl Transplantation Institute bMedical Scientist Training Program cDepartments of Surgery, Immunology, and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Walch
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
mesh_terms: D064591:Allografts / Q000098:blood supply* / Q000276:immunology*; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D003331:Coronary Vessels / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000276:immunology; D016030:Kidney Transplantation; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D011948:Receptors, Antigen, T-Cell