Allogeneic bone marrow grafts with high levels of CD4+CD25+FoxP3+ T cells can lead to engraftment failure

Authors

  • Stephan Fricke,

    Corresponding author
    1. Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
    2. Department of Immunology, Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany
    3. Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany
    • Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 01, 04103 Leipzig, Germany
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  • Katherina Rothe,

    1. Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
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  • Nadja Hilger,

    1. Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
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  • M. Ackermann,

    1. Department of Immunology, Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany
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  • Christopher Oelkrug,

    1. Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
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  • Christian Fricke,

    1. SRO AG, Medizinische Dienste SRO, Aarwangenstr. 20, 4900 Langenthal, Switzerland
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  • Uta Schönfelder,

    1. Division of Oncology and Hematology, Evangelic Diaconic Hospital, Leipzig, Germany
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  • Dietger Niederwieser,

    1. Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany
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  • Frank Emmrich,

    1. Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
    2. Department of Immunology, Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany
    3. Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany
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  • Ulrich Sack

    1. Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany
    2. Department of Immunology, Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany
    3. Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany
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Errata

This article is corrected by:

  1. Errata: Allogeneic bone marrow grafts with high levels of CD4+CD25+FoxP3+ T cells can lead to engraftment failure Volume 87, Issue 3, 279–280, Article first published online: 28 January 2015

  • Partial results have been presented in 8th Leipzig Research Festival for Life Sciences 2009, World Immune Regulation Meeting-III, 22-25 March 2009, Davos, Switzerland, at the Annual Meeting of the German Society of Hematology/Oncology, 06.10.2009, Heidelberg, Germany.

Abstract

Regulatory CD4+CD25+FoxP3+ T cells (Tregs) suppress immunological reactions. However, the effect of adding Tregs to hematopoietic stem cell grafts on recovery and graft versus host disease (GvHD) is unknown. Tregs from splenocytes of C57Bl/6 and Balb/c wild-type mice were isolated by MACS separation and analyzed by flow cytometry. Using a murine syngeneic transplantation model that clearly distinguishes between donor and host hematopoiesis, we showed that co-transplantation of bone marrow cells (BMCs) with high levels of Tregs leads to a 100% survival of the mice and accelerates the hematopoietic recovery significantly (full donor chimerism). In allogeneic transplantation, bone marrow and Tregs co-transplantation were compared to allogeneic bone marrow transplantation with or without the addition of splenocytes. Survival, leukocyte recovery, chimerism at days −2, 19, 33, and 61 for murine CD4, human CD4, HLA-DR3, murine CD3, murine CD8, murine Balb/c-H2Kd, murine C57Bl/6-H2Kb, and GvHD appearance were analyzed. Allogeneic bone marrow transplantation requires the addition of splenocytes to reach engraftment. Mice receiving grafts with bone marrow, splenocytes and high levels of allogeneic Tregs died within 28 days (hematopoietic failure). Here, we show also detailed flow cytometric data reagarding analysis of chimerism after transplantation in unique murine hematopoietic stem cell transplantation models. Our findings showed that the syngeneic co-transplantation of CD4+, CD25+, FoxP3+ T-cells and BMCs induced a stimulating effect on reconstitution of hematopoiesis after irradiation. However, in the allogeneic setting the co-transplantation of Tregs aggravates the engraftment of transplanted cells. © 2012 International Society for Advancement of Cytometry

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