Local Cognate Antigen in Kidney Allografts Promotes Tissue Resident Memory T Cell Maintenance
1Starzl Transplantation Institute, Pittsburgh, PA, 2Department of Immunology, University of Pittsburgh, Pittsburgh, PA
Meeting: 2022 American Transplant Congress
Abstract number: 481
Keywords: Antigen presentation, Graft-infiltrating lymphocytes, Kidney transplantation, T cells
Topic: Basic Science » Basic Science » 03 - Antigen Presentation / Allorecognition / Dendritic Cells
Session Information
Session Name: Antigen Presentation and Costimulation
Session Type: Rapid Fire Oral Abstract
Date: Tuesday, June 7, 2022
Session Time: 3:30pm-5:00pm
Presentation Time: 3:30pm-3:40pm
Location: Hynes Room 309
*Purpose: Our lab has demonstrated that tissue resident memory T cells (TRM cells) sustain chronic kidney allograft rejection in mice. It remains unknown how TRM cells survive in the graft. Given that cognate antigen persists in transplantation and plays a role in T cell migration and activation in the graft, we hypothesized that antigen is required for the maintenance of alloreactive TRM cells that drive chronic allograft rejection.
*Methods: Allogeneic (B6 x Balb/c) F1.Act-mOVA or F1 kidneys were transplanted into B6 recipients followed by adoptive transfer of OVA-specific T cell receptor-transgenic OT-I effector CD8 T cells 2 days post-transplant. F1.OVA kidney grafts express OVA, which contains the SIINFEKL peptide that is recognized by OT-I cells in the context of H2-Kb. F1 kidney grafts lack OVA. OT-I and P14 effector CD8 T cells were co-transferred into B6 recipients carrying F1.OVA grafts. Here, P14 cells recognize the antigen GP33-41, which is not present in the kidney graft. F1.OVA kidneys were transplanted into either CD11c-DTR:B6 or B6:B6 bone marrow (BM) chimeras. Diphtheria toxin (DT) was administered 4-6 weeks post-transplant. Three transplantation combinations were performed: A) F1.OVA graft to B6 recipient; B) F1.OVA graft to B6.Kb-/- recipient; and C) F1.OVA.Kb-/- graft to B6 recipient.
*Results: OT-I cells were found in significantly reduced numbers in F1 grafts 8 weeks post-transplant (F1=0.415K, F1.OVA=396K, p=0.0309). Similarly, OT-I cells were found in significantly greater numbers than P14 cells in F1.OVA grafts (OT-I=958K, P14=114K, p<0.0001). Administration of DT depleted graft-infiltrating CD11c+ dendritic cells, which decreased both OT-I and recipient polyclonal CD8 T cells (Fig. 1A-C). Graft function was preserved as assessed by serum creatinine measurement (Fig. 1D). When antigen presentation by either donor or recipient was removed, OT-I cell count and IFNγ production were significantly decreased (Fig. 2A, B).
*Conclusions: Local cognate antigen presented by CD11c+ dendritic cells contributes to the maintenance of TRM cells in the renal allograft. Therefore, interrupting antigen presentation is a potential approach to the prevention of chronic rejection.
To cite this abstract in AMA style:
Tieu R, Zeng Q, Zhao D, Manandhar P, Williams A, Abou-Daya K, Kane L, Shlomchik W, Oberbarnscheidt M, Lakkis F. Local Cognate Antigen in Kidney Allografts Promotes Tissue Resident Memory T Cell Maintenance [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/local-cognate-antigen-in-kidney-allografts-promotes-tissue-resident-memory-t-cell-maintenance/. Accessed December 3, 2024.« Back to 2022 American Transplant Congress