Cd137 on Host Dendritic Cells Fine-Tunes the Intesity of Donor T Cells in Systemic Alloinmmune Responses
1Department of Surgery, University of Ulsan College of Medicine, Ulsan, Korea, Republic of, 2University of Ulsan College of Medicine, Ulsan, Korea, Republic of, 3School of Biological Sciences, University of Ulsan, Ulsan, Korea, Republic of, 4Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan, Korea, Republic of
Meeting: 2022 American Transplant Congress
Abstract number: 926
Keywords: Autoimmunity, Co-stimulation, Inflammation, T cells
Topic: Basic Science » Basic Science » 09 - Signaling and Co-Stimulation
Session Information
Session Name: Co-Stimulation in Alloreactive Effector and Regulatory Responses
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: CD137 is a potent costimulatory receptor for CD8+ T cells but it also regulates dendritic cells (DCs) to suppress immune responses. In this study, we investigated the role of CD137 of dendritic cells in alloimmune responses.
*Methods: Balb/c à (Balb/c x C57BL/6)F1, BM12 à C57BL/6 GVHD , and DBA.c à (C56BL/6 x DBA/2)F1 GVHD models were used to investigate systemic alloimmune response in the spleen. Differentiation of donor T cells in the spleen were explored in WT or CD137-deficient recipients and control antibody-injected or anti-CD137 antibody-injected recipients. Disease patterns-systemic luypus erythematosus-like or systemic inflammation- were compared in recipient mice.
*Results: WT and CD137-/- recipients had different disease patterns in this model: systemic inflammation occurred in (Balb/c x C57BL/6)F1 recipients in which donor T cells were massively activated and engrafted, whereas there were deletion of donor T cells by activation-induced cell death (AICD) and autoantibody responses in ((Balb/c x C57BL/6)F1 CD137-/- recipients. This result indicates that CD137 signaling in host antigen-presenting cells functions as a fine-tuner for donor T cell activation. Two observations support this interpretation: 1) donor T cell-mediated systemic inflammation was induced in CD137-/- C57BL/6 mice that were transferred with less allogenic BM12 T cells; 2) Deletion of donor T cells, but neither systemic inflammation nor autoantibody responses, was observed in the ((Balb/c x C57BL/6)F1 or C57BL/6 host that received anti-CD137 agonist antibody. Further analysis showed that expression of cytokine genes in CD137-/- splenic DCs were dysregulated after transfer with donor T cells. Transfer of anti-CD137-primed DCs recovered systemic inflammation in CD137-/- recipients. Finally, we showed that there was impaired differentiation of mregDC (mature DC enriched in immunoregulatory molecules) in the spleen of CD137-/- recipients, while anti-CD137 antibody increased Treg cells through mregDCs in WT recipients.
*Conclusions: Our results suggest that CD137 signaling can suppress alloimmune and autoimmune responses by generating via mregDC.
To cite this abstract in AMA style:
Park S, Cho H, Kwon B, Lee J, Park H, Park J, Park K, Yoo K. Cd137 on Host Dendritic Cells Fine-Tunes the Intesity of Donor T Cells in Systemic Alloinmmune Responses [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/cd137-on-host-dendritic-cells-fine-tunes-the-intesity-of-donor-t-cells-in-systemic-alloinmmune-responses/. Accessed May 9, 2025.« Back to 2022 American Transplant Congress