Host NK Cell Allorecognition of Passenger Donor Lymphocytes Within Allografts Is Essential for Preventing Augmentation of Recipient Adaptive Alloimmunity
Department of Surgery, University of Cambridge, Cambridge, United Kingdom.
Meeting: 2015 American Transplant Congress
Abstract number: C3
Keywords: Allorecognition, Natural killer cells
Session Information
Session Name: Poster Session C: Antigen Presenting Cells in Alloimmune Responses/B Cells and Antibody in Alloimmune Responses
Session Type: Poster Session
Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background:
Memory T cells are now appreciated to reside in peripheral non-lymphoid tissue, but how their presence within solid organ allografts impacts upon transplant outcomes is not known. We have previously described how graft-versus-host (GVH) allorecognition by passenger CD4 T cells within MHC Class II-mismatched bm12 heart grafts provokes anti-nuclear humoral autoimmunity in B6 recipients. Here we aimed to examine how such GVH recognition impacts upon the alloresponse to more mismatched allografts
Methods:
An MHC class I and II mismatched murine model of cardiac transplantation was developed (bm12.Kd.IE to B6). Following transplantation, cellular and humoral responses against disparate antigens were assayed by ELISPOT and ELISA and the impact of GVH recognition assessed by depleting donor CD4 T cells prior to graft procurement. Anti-nuclear autoantibody development was assayed by HeP-2 indirect immunofluorescence. The role of recipient NK cells was examined by depletion with anti-NK1.1 antibody.
Results:
Bm12.Kd.IE heart grafts provoked strong germinal centre allo- and auto-antibody responses in B6 recipients and developed allograft vasculopathy. In contrast, heart grafts from CD4 T cell-depleted donors developed only minimal vasculopathy, and the alloantibody responses were weaker, without observable autoantibody. Bm12.Kd.IE CD4 T cells survive long term when transferred to RAG hosts suggesting that avoidance of killing by host NK cells may be essential for autoantibody development. In support, in a model of alloantibody mediated vasculopathy, depletion of NK cells from a B6 recipient of a Balbc heart graft resulted in the development of autoantibody, amplification of the alloantibody response and rapid allograft rejection. This amplification was abrogated by depleting donor CD4 T cells.
Conclusions:
Although host adaptive immunity is expected to effect destruction of passenger lymphocytes within heart allografts, this occurs too slowly to prevent GVH-mediated augmentation of the alloresponse to the graft. Rapid killing of donor lymphocytes by host alloreactive NK cells is instead essential. Passenger CD4 lymphocytes may therefore contribute to chronic rejection in recipients who receive an allograft that does not prompt innate NK cell recognition.
To cite this abstract in AMA style:
Ali J, Harper I, Negus M, Bolton E, Saeb-Parsy K, Bradley J, Pettigrew G. Host NK Cell Allorecognition of Passenger Donor Lymphocytes Within Allografts Is Essential for Preventing Augmentation of Recipient Adaptive Alloimmunity [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/host-nk-cell-allorecognition-of-passenger-donor-lymphocytes-within-allografts-is-essential-for-preventing-augmentation-of-recipient-adaptive-alloimmunity/. Accessed May 31, 2025.« Back to 2015 American Transplant Congress