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Immunology

Immunosuppressive CD14+HLA-DRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation

Leukemia volume 27, pages 377–388 (2013)Cite this article

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Abstract

Myeloid-derived suppressor cells (MDSCs) have emerged as a heterogeneic immunoregulatory population that can expand in response to inflammatory signals. Predominantly studied in cancer, MDSCs suppress T cells utilizing various mechanisms. In allogeneic hematopoietic stem cell transplantation (allo-HSCT) therapy-related toxicity and alloreactivity increase inflammatory cytokines that might favor an MDSC accumulation. To address this question, circulating CD14+HLA-DRlow/neg cells were studied retrospectively in 51 allo-HSCT patients. These cells represent one of the few well-described human MDSC subsets under physiological and pathological conditions. The frequency of CD14+HLA-DRlow/neg cells was significantly increased after allo-HSCT, especially in patients with acute graft-versus-host disease. Compared to healthy donor cells they were pSTAT1low (phosphorylated signal transducer and activator of transcription) and indoleamine 2,3-dioxygenase (IDO)high. Serum levels of granulocyte colony-stimulating factor and interleukin-6, which both have been linked to MDSC induction, correlated positively with the frequency of CD14+HLA-DRlow/neg cells. In vitro dysfunction of patient T cells, such as reduced proliferative capacity or CD3ζ-chain expression, was rescued by blocking the IDO activity of CD14+HLA-DRlow/neg cells. Overall, we identified a T-cell-suppressive monocytic population that expands after allo-HSCT. The mechanisms responsible for such accumulation remain to be elucidated. It will be of great interest to prospectively investigate the influence of these cells on the graft-versus-tumor and -host reaction.

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Acknowledgements

KLB was supported by grants from the Swedish Cancer Foundation (110315), the Children’s Cancer Foundation (08/071), the Swedish Research Council (K2011-??X-20742–04–6), the Tobias Foundation, VINNOVA (2010–00501), the Stockholm City Council (ALF 20110152) and the Cancer Society in Stockholm. DM was supported by the German Research Association (DFG), the Interdisciplinary Center of Clinical Research (IZKF) Erlangen and the University of Erlangen-Nuremberg (ELAN grant).

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Author notes

  1. D Mougiakakos and R Jitschin: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden

    D Mougiakakos, R Jitschin, L von Bahr, B Sundberg & K Le Blanc

  2. Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany

    D Mougiakakos, R Gary & A Gerbitz

  3. Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden

    I Poschke

  4. Department of Hematology, Karolinska University Hospital and Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden

    L von Bahr, P Ljungman & K Le Blanc

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Mougiakakos, D., Jitschin, R., von Bahr, L. et al. Immunosuppressive CD14+HLA-DRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation. Leukemia 27, 377–388 (2013). https://doi.org/10.1038/leu.2012.215

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