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

Follicular Helper T Cell Modulation by Costimulation Blockade Prevents Antibody-Mediated Rejection in Nonhuman Primate Renal Transplantation

J. Kwun, E. Page, A. Gibby, J. Hong, A. Farris, A. Adams, N. Iwakoshi, C. Larsen, A. Kirk, S. Knechtle

Surgery, Emory University, Atlanta, GA
Pathology, Emory University, Atlanta, GA

Meeting: 2013 American Transplant Congress

Abstract number: 474

Related Abstracts
  • Costimulation Blockade and Bortezomib to Desensitize Rhesus Macaque and Prolong Renal Allograft Survival
  • Effect of Belatacept on Follicular Helper T Cell and Humoral Response in Sensitized Rhesus Macaques, The

[Background] De novo donor-specific antibody (DSA) after organ transplantation promotes antibody-mediated rejection (AMR) and causes late graft loss. Nearly a third of transplant recipients develop de novo antibodies, for which no established therapies are effective at preventing. Previously, we demonstrated that depletion using anti-CD3 immunotoxin (IT) combined with Tacrolimus and Alefacept (AMR regimen) reliably induced early DSA production with antibody-mediated injury in a nonhuman primate kidney transplant model.

[Methods] All rhesus macaques received the AMR regimen of CD3-IT × 4 days, alefacept × 8 weeks, and tacrolimus maintenance. Five animals were assigned as positive AMR controls, four received additional belatacept (20mg/kg weekly × 8 weeks), and four received additional anti-CD40 mAb 2c10 (20mg/kg weekly × 8 weeks).

[Results] Notably, production of early de novo DSA was completely attenuated (*p<0.05) at 4 and 6 weeks post transplantation with additional Belatacept (n=4) or 2C10 (n=4) treatment compared to the AMR control group (n=5). In accordance with this, while positive controls experienced a decrease in peripheral IgM+CD20+ B cells by day 28, bela- and 2c10-added groups maintained a predominant population of IgM+CD20+ B cells, potentially indicating decreased isotype switching. Central memory T cells (CD4+CD28+CD95+) as well as follicular helper T (Tfh) cells (PD-1hiCD4+CD3+) were decreased in both bela-added and 2c10-added groups compared to the AMR controls. In analyzing Tfh cells and germinal center reactions in situ, immunostained lymph nodes further revealed a reduction of B cell clonal expansion (% of Ki67+CD20+ in the follicle; 2.11±0.31 or 3.37±2.34 vs. 9.08±2.71%; p<0.05)), Tfh Cells (# of PD-1hiCD4+ per mm2; 33.80±24.23 or 195.90±242.81 vs. 502.72±169.34 mm2;p<0.05), and IL-21 production (% CD3+IL-21+ area in the follicle; 2.52±0.53 or 3.54±1.01 vs. 7.42±2.23%; P<0.05) inside germinal centers with additional belatacept or 2C10 treatment compared to AMR controls.

[Conclusions] Here we provide evidence that Belatacept and 2C10 selectively suppresses the humoral response via regulating follicular helper T cells (Tfh) and prevents AMR in this non-human primate model. These results support the translation of selective supplementation with belatacept for AMR prevention.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Kwun J, Page E, Gibby A, Hong J, Farris A, Adams A, Iwakoshi N, Larsen C, Kirk A, Knechtle S. Follicular Helper T Cell Modulation by Costimulation Blockade Prevents Antibody-Mediated Rejection in Nonhuman Primate Renal Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/follicular-helper-t-cell-modulation-by-costimulation-blockade-prevents-antibody-mediated-rejection-in-nonhuman-primate-renal-transplantation/. Accessed January 22, 2021.

« Back to 2013 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.
  • Penis Transplantation: First U.S. Experience.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • 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.
    • 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.