Application of Allogeneic Bone Marrow Cells in View of Residual Alloreactivity: Sirolimus but Not Cyclosporine Evolves Tolerogenic Properties

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Apr 4

PMID 25836261

Citations 1

Authors

Kai Timrott

Florian W R Vondran

Hueseyin Bektas

Jurgen Klempnauer

Mark D Jager

Affiliations

Soon will be listed here.

Abstract

Background: Application of bone marrow cells (BMC) is a promising strategy for tolerance induction, but usually requires strong depletion of the host immune system. This study evaluates the ability of immunosuppressants to evolve tolerogenic properties of BMC in view of residual alloreactivity.

Methods: The rat model used a major histocompatibility complex (MHC) class II disparate bone marrow transplantation (BMT) setting (LEW.1AR1 (RT1auu) → LEW.1AR2 (RT1aau)). Heart grafts (LEW.1WR1 (RT1uua)) were disparate for the complete MHC to recipients and for MHC class I to BMC donors. Limited conditioning was performed by total body irradiation of 6 Gy. Cyclosporine (CsA) or Sirolimus (Srl) were administered for 14 or 28 days. Transplantation of heart grafts (HTx) was performed at day 16 or at day 100 after BMT. Chimerism and changes in the T cell pool were detected by flow cytometry.

Results: Mixed chimeras accepted HTx indefinitely, although the composition of the regenerated T cell pool was not changed to a basically donor MHC class II haplotype. Non-chimeric animals rejected HTx spontaneously. BMC recipients, who received HTx during T cell recovery at day 16, accepted HTx only after pre-treatment with Srl, although chimerism was lost. CsA pre-treatment led to accelerated HTx rejection as did isolated application of BMC.

Conclusion: Srl evolves tolerogenic properties of allogeneic BMC to achieve indefinite acceptance of partly MHC disparate HTx despite residual alloreactivity and in particular loss of chimerism.

Citing Articles

The importance of MHC class II in allogeneic bone marrow transplantation and chimerism-based solid organ tolerance in a rat model.

Timrott K, Beetz O, Oldhafer F, Klempnauer J, Vondran F, Jager M PLoS One. 2020; 15(5):e0233497.

PMID: 32442182 PMC: 7244129. DOI: 10.1371/journal.pone.0233497.

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