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CD4+ T cell counts reflect the immunosuppressive state of CD4 helper cells in patients after allogeneic stem cell transplantation

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Abstract

The recovery of the host immune system after allogeneic hematopoietic stem cell transplantation is pivotal to prevent infections, relapse, and secondary malignancies. In particular, numerical CD4+ T cells reconstitution is delayed and CD4 helper cell function is considered impaired as a consequence of the transplant procedure and concomitant immunosuppressive medication. From HIV/AIDS patients, it is known that numerical and functional CD4 defects increase the risk of opportunistic infections. However, and in contrast to patients with HIV, anti-infective prophylaxis after allogeneic transplantation is usually given for 6 months depending on immunosuppressive medication and existing graft-versus-host disease but independently of absolute CD4+ T cells counts. We hypothesized that a qualitative T cell defect is existing after allogeneic transplantation, especially in patients with delayed immune-reconstitution. Applying transcriptional as well as functional approaches, we show that CD4+ T cells with delayed recovery have a distinct transcriptional profile and cluster differently from T cells originated from patients with completed immune recovery. Moreover, inhibitory signatures are substantially enriched within the transcriptional profile of these T cells translating to functional defects and impaired interleukin 2 production. In addition to time after transplant, CD4+ T cells numbers should be considered for the decision to stop or maintain antimicrobial prophylaxis in patients after allogeneic stem cell transplantation.

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Acknowledgments

Informed consent was obtained from all healthy donors and from patients for being included in the study.

Conflict of interest

The authors have nothing to disclose in relation to the manuscript submitted.

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Authors and Affiliations

  1. Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany

    Udo Holtick, Lukas P. Frenzel, Alexander Shimabukuro-Vornhagen, Sebastian Theurich, Julia Claasen, Christof Scheid, Michael von Bergwelt-Baildon, Clemens M. Wendtner & Jens M. Chemnitz

  2. Algorithmic Bioinformatics, Bonn-Aachen International Center for IT, Bonn, Germany

    Holger Fröhlich

  3. Department I of Internal Medicine, Klinikum Schwabing, Academic Teaching Hospital of University of Munich, Munich, Germany

    Clemens M. Wendtner

  4. Cologne Interventional Immunology, University of Cologne, Cologne, Germany

    Udo Holtick

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  1. Udo Holtick
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  2. Lukas P. Frenzel
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  3. Alexander Shimabukuro-Vornhagen
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  4. Sebastian Theurich
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  5. Julia Claasen
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  10. Jens M. Chemnitz
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Corresponding author

Correspondence to Udo Holtick.

Additional information

Udo Holtick, Lukas P. Frenzel, Clemens M. Wendtner, and Jens M. Chemnitz contributed equally to the manuscript.

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Holtick, U., Frenzel, L.P., Shimabukuro-Vornhagen, A. et al. CD4+ T cell counts reflect the immunosuppressive state of CD4 helper cells in patients after allogeneic stem cell transplantation. Ann Hematol 94, 129–137 (2015). https://doi.org/10.1007/s00277-014-2166-1

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  • DOI: https://doi.org/10.1007/s00277-014-2166-1

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