Original Article

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

  1. Stephan Fricke1,2,3,*,
  2. Katherina Rothe1,
  3. Nadja Hilger1,
  4. M. Ackermann2,
  5. Christopher Oelkrug1,
  6. Christian Fricke4,
  7. Uta Schönfelder5,
  8. Dietger Niederwieser3,
  9. Frank Emmrich1,2,6,
  10. Ulrich Sack1,2,6

Article first published online: 20 APR 2012

DOI: 10.1002/cyto.a.22061

Issue

Cytometry Part A

Cytometry Part A

Volume 81A, Issue 6, pages 476–488, June 2012

Additional Information

How to Cite

Fricke, S., Rothe, K., Hilger, N., Ackermann, M., Oelkrug, C., Fricke, C., Schönfelder, U., Niederwieser, D., Emmrich, F. and Sack, U. (2012), Allogeneic bone marrow grafts with high levels of CD4+CD25+FoxP3+ T cells can lead to engraftment failure. Cytometry, 81A: 476–488. doi: 10.1002/cyto.a.22061

Author Information

  1. 1

    Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Leipzig, Germany

  2. 2

    Department of Immunology, Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany

  3. 3

    Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany

  4. 4

    SRO AG, Medizinische Dienste SRO, Aarwangenstr. 20, 4900 Langenthal, Switzerland

  5. 5

    Division of Oncology and Hematology, Evangelic Diaconic Hospital, Leipzig, Germany

  6. 6

    Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany

*Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 01, 04103 Leipzig, Germany

  1. †

    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.

Publication History

  1. Issue published online: 21 MAY 2012
  2. Article first published online: 20 APR 2012
  3. Manuscript Accepted: 29 MAR 2012
  4. Manuscript Revised: 8 FEB 2012
  5. Manuscript Received: 19 AUG 2011

Funded by

  • German Federal Ministry of Education and Research. Grant Numbers: BMBF 0313452, PtJ-Bio, 0313909

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Keywords:

  • hematopoietic stem cell transplantation;
  • chimersim;
  • flow cytometry;
  • triple transgenic mice;
  • regulatory T cells;
  • bone marrow cells

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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