ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Advanced Search

p40 Homodimer Indirectly Induce Proliferation of Endogenous Donor-Reactive Memory CD8 T Cells within High-Risk Allografts via IL-15 Signaling

H. Tsuda, A. Valujskikh, R. Fairchild

Inflammation and Immunity, Cleveland Clinic, Cleveland, OH

Meeting: 2019 American Transplant Congress

Abstract number: 492

Keywords: Co-stimulation, Heart/lung transplantation, Ischemia, T cell graft infiltration

Session Information

Date: Tuesday, June 4, 2019

Session Name: Concurrent Session: Acute Rejection: Basic

Session Time: 2:30pm-4:00pm

 Presentation Time: 3:30pm-3:42pm

Location: Room 313

Related Abstracts
  • p40 Homodimer Induced Proliferation of Endogenous Donor-Reactive Memory CD8 T Cells within High Risk Allografts Requires Memory CD8 T Cell Expression of CD122
  • Graft Dendritic Cell p40 Homodimers Activate Donor-Reactive Endogenous Memory CD8 T Cells within Higher Risk Allografts

*Purpose: Increasing the duration of cold ischemic storage (CIS) from 0.5 to 8 hrs prior to transplant induces the increased proliferation of endogenous donor-reactive CD4 and CD8 T cells in mice cardiac allografts within 24 hours of reperfusion and the effector functions of the activated memory CD8 T cells to directly mediate CTLA-4Ig-resistant rejection of the higher risk allografts. Our previous studies indicated this increased memory CD8 T cell proliferation within high-risk allografts requires CD4 T cell help via CD40-CD154 interactions with graft dendritic cells to induce IL-12p40 homodimer (p40 HD) production that is required to drive the memory CD8 T cell proliferation. The goal of the current study was to test if p40HD directly or indirectly stimulate this CD8 T cell proliferation within allografts subjected to 8hrs CIS and to investigate the mechanisms of p40 HD driven CD8 T cell proliferation.

*Methods: To test this, we use a heterotopic cardiac model which transplanted complete MHC mismatched heart allograft subjected to various time of CIS prior to transplant.

*Results: Endogenous memory CD8 T cells within highly ischemic allografts expressed both IL12Rβ1 and β2. However, most proliferating CD8 T cells did not express IL12Rβ1 needed for p40 HD mediated signaling. Moreover, endogenous memory CD8 T cells isolated from allografts did not proliferate ex vivo when cultured with p40 HD. These results suggested p40 HD may provoke memory CD8 T cell proliferation within the higher risk allografts by indirectly binding to IL-12Rβ1 expressing cells leading us to investigate other candidate factors to drive this memory CD8 T cell proliferation. qPCR analysis indicated increased mRNA expression of IL2Rα (CD25), β(CD122) and IL15Rα in infiltrating CD8 T cells purified from allografts subjected to prolonged vs. minimal CIS on day 2 post-transplant. ELISA indicated longer CIS time markedly increased IL-12p40 and IL-15 protein in the allografts and these increases were dependent on recipient CD4 T cells. Blocking of p40 or IL-15 signaling with anti-p40 or anti-CD122 mAb inhibited endogenous memory CD8 T cell proliferation within high-risk cardiac allografts in CTLA-4Ig conditioned recipients and extended the survival of the high-risk allografts from days 16-23 to days 40-72 (anti-p40 mAb) and days 24-97 (anti-CD122 mAb).

*Conclusions: These results suggest that p40 HD produced by graft DCs stimulated the production of proliferative cytokines such as IL-15, which directdly stimulates endogenous donor-reactive memory CD8 T cell proliferation within allografts subjected to 8 hours CIS.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Tsuda H, Valujskikh A, Fairchild R. p40 Homodimer Indirectly Induce Proliferation of Endogenous Donor-Reactive Memory CD8 T Cells within High-Risk Allografts via IL-15 Signaling [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/p40-homodimer-indirectly-induce-proliferation-of-endogenous-donor-reactive-memory-cd8-t-cells-within-high-risk-allografts-via-il-15-signaling/. Accessed March 8, 2021.

« Back to 2019 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • Penis Transplantation: First U.S. Experience.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus: A Case Report
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2021 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy

loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.