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Myelodysplasias

Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40–CD40L interactions with T helper cells

Leukemia volume 21, pages 2411–2419 (2007)Cite this article

Abstract

Immune mechanisms have been shown to contribute to the process of myelodysplastic syndromes (MDS)-related bone marrow (BM) failure. The aim of this study was to evaluate the possible contribution of activated monocytes through CD40–CD40L(CD154) interactions with activated T helper cells. We demonstrated in 77 predominantly lower risk MDS patients that the CD40 receptor was expressed significantly higher on monocytes and that CD40L was expressed significantly higher on T helper cells in peripheral blood (PB) and BM. Increased levels of CD40 and CD40L were detected in the same patients. In addition, stimulation of the CD40 receptor on purified PB monocytes led to a significantly higher tumor necrosis factor alpha production in patients. Co-culture of BM mononuclear cells of 21 patients in the presence of a blocking CD40 monoclonal antibody (ch5D12) led to a significant increase in the number of colony-forming units. A correlation was seen between increased CD40 expression on monocytes with patients’ age below 60 years and with the cytogenetic abnormality trisomy 8. These results demonstrate that CD40 expression on monocytes may identify a subgroup of MDS patients in whom immune-mediated hematopoietic failure is part of the disease process. As such, the CD40–CD40L-based activation of monocytes might be a target to counteract MDS-related BM failure.

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Acknowledgements

SM, CV and MD are supported by research fundings from the Research Foundation-Flanders (FWO). SM is a research fellow and MD is a clinical professor of the FWO. LB contributed vital new reagents (clone 64 and ch5D12) to perform this research.

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Authors and Affiliations

  1. Department of Hematology, University of Leuven, Leuven, Belgium

    S Meers, M Boogaerts, G Verhoef, C Verfaillie & M Delforge

  2. Stem Cell Institute, University of Leuven, Leuven, Belgium

    S Meers, C Verfaillie & M Delforge

  3. Department of Immunology, University of Leuven, Leuven, Belgium

    A Kasran

  4. PanGenetics BV, Utrecht, The Netherlands

    L Boon

  5. Department of Hematology, Sint-Augustinus Hospital, Wilrijk, Belgium

    J Lemmens

  6. Department of Hematology, Jules Bordet Institute, Brussels, Belgium

    C Ravoet

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  1. S Meers
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Correspondence to S Meers.

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Meers, S., Kasran, A., Boon, L. et al. Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40–CD40L interactions with T helper cells. Leukemia 21, 2411–2419 (2007). https://doi.org/10.1038/sj.leu.2404940

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