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

Flt3 Ligand Induces STAT3-Independent Expansion and Activation of Myeloid-Derived Suppressor Cells Able To Promote Heart Allograft Survival

B. Rosborough, Q. Liu, D. Raich-Regue, B. Matta, L. Mathews, A. Thomson, H. Turnquist

Surgery, Starzl Transplant Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA

Meeting: 2013 American Transplant Congress

Abstract number: C1288

Related Abstracts
  • Arachidonate Lipoxygenase Controls the Suppressive Function of Myeloid Derived Suppressor Cells
  • Complement Component 3 (C3) Participates in Induction of Myeloid Suppressor Cells

Introduction: Fms-like tyrosine kinase 3 ligand (Flt3L) is essential for myeloid cell homeostasis, particularly dendritic cells (DC), and acts through STAT3 to promote DC expansion. Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immunoregulatory CD11b+Gr1+ immature myeloid cells that suppress T cell responses and are required for experimental tolerance induction after heart transplantation. However, the influence of Flt3L in vivo on the expansion and activation of MDSC has not been examined. Due to the ability of Flt3L to augment expansion of multiple myeloid cell populations, we hypothesized that Flt3L administration would expand immunosuppressive MDSC able to promote heart transplant survival.

Methods: BALB/c mice were given recombinant human Flt3L (10 Μg/d i.p.) daily for 10 d, with or without STAT3 inhibitor S31-201 (5 mg/kg i.p.). Splenic CD11c+ and Gr1+ cells were isolated by immunomagnetic bead selection and tested as stimulators or suppressors, respectively, in mixed leukocyte reactions with CD3+ T cell responders. BALB/c recipients were given syngeneic MDSC (5×106) one day prior to heterotopic transplantation of C57BL/6 hearts. Survival was monitored by abdominal palpation and rejection confirmed histologically.

Results: Flt3L increased the absolute number and frequency of splenic DC (CD11b+CD11c+) and MDSC (CD11b+Gr1+). Although DC from Flt3L-treated mice stimulated allogeneic T cell proliferation more than control DC, MDSC from these mice were more potent suppressors of T cell proliferation than control MDSC. Flt3L activated MDSC, which required IDO and HO-1 for T cell suppression. Although STAT3 is thought to be critical for MDSC expansion and activation, STAT3 inhibition blocked DC expansion but augmented Flt3L-mediated MDSC expansion. Notably, STAT3 inhibition did not alter Flt3L-expanded MDSC suppressive function. Syngeneic Flt3L-expanded MDSC, but not control MDSC, administered one day before transplantation of fully MHC-mismatched heart grafts prolonged survival significantly in the absence of immunosuppression.

Conclusions: These data provide the first demonstration that transfer of Flt3L-expanded MDSC prolongs cardiac allograft survival. Furthermore, we identify a novel immunomodulatory capacity of Flt3L for expansion of functional MDSC in a STAT3-independent manner.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Rosborough B, Liu Q, Raich-Regue D, Matta B, Mathews L, Thomson A, Turnquist H. Flt3 Ligand Induces STAT3-Independent Expansion and Activation of Myeloid-Derived Suppressor Cells Able To Promote Heart Allograft Survival [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/flt3-ligand-induces-stat3-independent-expansion-and-activation-of-myeloid-derived-suppressor-cells-able-to-promote-heart-allograft-survival/. Accessed February 27, 2021.

« Back to 2013 American Transplant Congress

Most Viewed Abstracts

  • This Week
  • This Month
  • All Time
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • 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.
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?
  • Kidney Dialysis after Heart Transplantation: The Short and Long Term Outcomes
  • 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.
  • A Decade of Donor-Derived Disease: A Report of the OPTN Ad Hoc Disease Transmission Advisory Committee (DTAC).
  • Is There a Difference Between DCD and DBD Kidney Transplantation with Similar KDPI?

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.