title: CD8+ Effector T Cell Migration to Pancreatic Islet Grafts Is Dependent on Cognate Antigen Presentation by Donor Graft Cells.
abstract: Pancreatic islet transplantation is a promising therapy for diabetes, but acute rejection of the islets by host effector T cells has hindered clinical application. In this study, we addressed the mechanisms of CD8(+) effector T cell migration to islet grafts because interrupting this step is key to preventing rejection. We found that effector T cell migration to revascularized islet transplants in mice is dependent on non-self Ag recognition rather than signaling via Gαi-coupled chemokine receptors. Presentation of non-self Ag by donor cells was necessary for migration, whereas Ag presentation by recipient cells was dispensable. We also observed that deficiency of SKAP1, an immune cell adaptor downstream of the TCR and important for integrin activation, prolongs allograft survival but does not reduce effector T cell migration to the graft. Therefore, effector T cell migration to transplanted islets is Ag driven, not chemokine driven, but SKAP1 does not play a critical role in this process.
authors.affiliation: Tsinghua University School of Medicine, Beijing 100084, China; Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Qianqian
authors.identifier: 0000-0002-3297-5326
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Hehua
authors.initials: H
authors.lastname: Dai
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Karim M
authors.identifier: 0000-0002-2607-7044
authors.initials: KM
authors.lastname: Yatim
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Khodor
authors.identifier: 0000-0001-8788-2728
authors.initials: K
authors.lastname: Abou-Daya
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Williams
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Martin H
authors.identifier: 0000-0003-2040-809X
authors.initials: MH
authors.lastname: Oberbarnscheidt
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261;
authors.forename: Geoffrey
authors.identifier: 0000-0003-0771-4009
authors.initials: G
authors.lastname: Camirand
authors.affiliation: Cell Signaling Section, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom;
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Rudd
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261; and Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261 lakkisf@upmc.edu.
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D023421:Models, Animal