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

2B4 Over-Expression Impairs Donor-Reactive CD8+ T Cell Proliferation and Accumulation Following Transplantation.

S. Laurie, D. Liu, M. Ford.

Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.

Meeting: 2016 American Transplant Congress

Abstract number: 542

Keywords: Co-stimulation, Immunosuppression, Mice, T cell reactivity

Session Information

Date: Tuesday, June 14, 2016

Session Name: Concurrent Session: Novel Approaches and Potential Targets for Promoting Tolerance: Animal Models

Session Time: 4:30pm-6:00pm

 Presentation Time: 5:18pm-5:30pm

Location: Room 310

Related Abstracts
  • Overexpression of 2B4 Inhibits the Expansion and Function of Donor-Reactive CD8+ T Cells in Selective Lymphoid Compartments
  • CTLA4 Negatively Regulates Donor-Reactive CXCR5+PD1+ T Follicular Helper Cell Responses Following Transplantation.

T cell function is tightly regulated by a fine balance of coinhibitory signals, including those transduced by 2B4 (SLAMf4, CD244), an immunoglobulin-superfamily member constitutively expressed on NK cells and induced on some T cell subsets. Recent studies from our group suggest that 2B4 plays a functional role in the inhibition of donor-reactive CD8+ T cell responses in vivo in the setting of selective CD28 blockade. These findings raise the possibility that 2B4 itself may be a therapeutic target to attenuate allograft rejection. Thus, we hypothesized that augmenting 2B4 signaling would attenuate graft-specific CD8+ T cell responses following transplantation. To test this, we created 2B4 retrogenic (2B4rg) donor-reactive CD8+ OT-I T cells which ectopically express 2B4. 2B4 retrogenic Thy1.1+ CD8+ T cells (or empty vector-transduced controls) were adoptively transferred into naïve animals. Mice then received an OVA-expressing skin graft and were sacrificed ten days later. Data show that constitutive 2B4 expression results in significantly reduced accumulation of antigen-specific CD8+ T cells in the spleen 10 days post-transplantation as compared to wild-type pMY controls (1.23×106 +/- 4.27×105 vs. 6.51×106 +/- 2.81×106, respectively, p=0.0267). This was not due to differences in expression of the 2B4 ligand CD48 or the T cell activation or exhaustion markers CD44, KLRG-1, CD127, TIM-1, PD-1, and LAG-3. Further, the differences in donor-reactive CD8+ T cell accumulation were not explained by increased cell death, as we observed no difference in frequencies of Annexin V+ 7-AAD+ apoptotic cells between 2B4rg donor-reactive CD8+ T cells and empty vector controls. Instead, we observed a marked reduction in the proliferation of the CD8+ Thy1.1+ 2B4rg cells when compared to controls as measured by CellTrace Violet (CTV) analysis. Specifically, the 2B4rg CD8+ Thy1.1+ population contained a higher frequency of CTVhi undivided cells as compared to non-retrogenic controls (13.62% +/- 0.5476 vs. 2.642% +/- 1.167, respectively, p=0.0022), suggesting that overexpression of 2B4 on donor-reactive CD8+ T cells results in reduced recruitment into the response. Interestingly, 2B4rg cells still differentiated into cytokine-producing effectors despite their inability to divide normally. These findings suggest that engaging the 2B4 coinhibitory pathway could represent a novel therapeutic strategy to prevent the expansion of alloreactive CD8+ T cells following transplantation.

CITATION INFORMATION: Laurie S, Liu D, Ford M. 2B4 Over-Expression Impairs Donor-Reactive CD8+ T Cell Proliferation and Accumulation Following Transplantation. Am J Transplant. 2016;16 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Laurie S, Liu D, Ford M. 2B4 Over-Expression Impairs Donor-Reactive CD8+ T Cell Proliferation and Accumulation Following Transplantation. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/2b4-over-expression-impairs-donor-reactive-cd8-t-cell-proliferation-and-accumulation-following-transplantation/. Accessed January 19, 2021.

« Back to 2016 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.
  • Subtherapeutic Low Tacrolimus Trough Levels (≤3.5 Ng /ml) Are A Risk Factor For Acute Rejection And Creatinine Doubling.
  • Home
  • Penis Transplantation: First U.S. Experience.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Search
  • 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.