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

Engineering a “Hybrid Thymus” to Promote Transplant Tolerance.

S. AlFadil,1 M.-J. Kim,2 M. Iglesias Lozano,1 B. Oh,1 W. Lee,1 G. Brandacher,1 T. Serworld,2 G. Raimondi.1

1Plastic & Recnstructive Surgery, Johns Hopkins Medical Institute, Baltimore, MD
2Joslin Diabetes Center, Boston, MA.

Meeting: 2016 American Transplant Congress

Abstract number: 88

Keywords: Engraftment, Epithelial cells, Negative selection, Thymic tolerance

Session Information

Date: Sunday, June 12, 2016

Session Name: Concurrent Session: Allograft Tolerance 1: Animal Models

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

 Presentation Time: 5:30pm-5:42pm

Location: Room 306

Related Abstracts
  • Chimeric Thymus Versus Antigen Presenting Thymus for the Induction of Tolerance: Donor DCs in Vascularized Thymus Grafts Play an Essential Role in the Induction of Tolerance
  • Thymic Transplantation to Determine Mechanisms of Thymic Involution: Insulin-Like Growth Factor 1 Receptor and Forkhead Box Protein N1 in the Thymus Play a Role in Maintaining the Juvenile Thymus

Purpose: Targeting the process of central (thymic) selection of developing T lymphocytes is the key tolerogenic mechanism of bone marrow transplantation (BM-Tx)-based protocols for transplant tolerance induction. However, they are not amenable to most transplant recipients. Thymic Epithelial Cells (TEC), a population of stromal cells residing in the thymus, exert a major contribution to central selection. However, donor TEC do not develop following BM-Tx protocols. Therefore, we propose a new immunomodulatory strategy based on generating a donor-recipient “Hybrid Thymus”, through donor TEC engraftment into the recipient thymus, to re-engineer the thymic microenvironment that selects developing thymocytes and achieve dominant central tolerance.

Methods: We optimized a protocol for isolating TEC via a combination of negative and positive selection. Purified BALB/c TEC (from 3-12 day old mice) were injected intrathymically into C57BL/6 with or without co-stimulation blockade (CoB: CTLA4-Ig +/- anti-CD40 mAb). TEC survival post-injection was assessed via immunofluorescent staining of thymic sections and peripheral T cells analyzed for changes in TCR Vβ11 expression– a marker of negative selection.

Results: Our optimized purification protocol yields an average 70% TEC purity. Injection of BALB/c TEC in otherwise unmanipulated animals resulted in minimal survival by POD21, suggesting an absence of intrinsic immunomodulatory capacity of these cells. However, CTLA4-Ig co-administration exerted a significant protection with a higher survival at POD21 and 28. In this latter treatment group, the percentage of peripheral Vβ11+ T cells on d21 was significantly decreased indicating actuation of negative selection by the engrafted donor TEC. The full CoB regimen provided the highest survival rate at all time points, indicating the need for a complementary treatment to promote alloTEC engraftment. We are currently investigating the long term TEC survival and the impact on host alloreactivity.

Conclusion: Our preliminary data show that the thymic engraftment, survival, and function of allogenic TEC can be promoted by CoB. These exciting results indicate that engineering a donor-recipient Hybrid Thymus is feasible and has the potential to promote a dominant regulation of alloreactivity that could be conducive to transplant tolerance induction.

CITATION INFORMATION: AlFadil S, Kim M.-J, Iglesias Lozano M, Oh B, Lee W, Brandacher G, Serworld T, Raimondi G. Engineering a “Hybrid Thymus” to Promote Transplant Tolerance. Am J Transplant. 2016;16 (suppl 3).

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

AlFadil S, Kim M-J, Lozano MIglesias, Oh B, Lee W, Brandacher G, Serworld T, Raimondi G. Engineering a “Hybrid Thymus” to Promote Transplant Tolerance. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/engineering-a-hybrid-thymus-to-promote-transplant-tolerance/. Accessed March 1, 2021.

« Back to 2016 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Low GFR after Kidney Donation Is Not Chronic Kidney Disease
  • Live Related Kidney Transplant Experience in Abuja, Nigeria – First Eight Cases Ever.
  • Left-Sided Donor Nephrectomy Predisposes Living Kidney Donors to Latent Adrenal Insufficiency with Symptoms of Fatigue and Inferior Quality of Life.
  • Home
  • 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

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.