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Signal Transduction and Cytokines

Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in acute myelogenous leukemia blasts, through secretion of inflammatory cytokines: dominant role for TNFβ, in concert with IFNγ

Leukemia volume 20, pages 1992–2001 (2006)Cite this article

Abstract

We have previously reported that alloreaction can lead to activation of dendritic cells through secretion of inflammatory cytokines. Here, we addressed whether alloreaction-derived cytokines may also lead to acute myelogenous leukemia (AML) blast differentiation. With this aim, supernatant (sn) harvested from major or minor histocompatibility antigen-mismatched mixed lymphocyte reaction (MLR) were used to culture French American Bristish (FAB) type M4 or M5 AML blasts. Our results showed that the secreted factors induced upregulation of CD40, CD54, and/or HLA molecules in AML blasts. Protein fractionation, blockade experiments and exogenous cytokine reconstitution demonstrated the involvement of TNF in the upregulation of CD54, CD40 and HLA-class II molecules, and of IFNγ in the increase of HLA-class I and class II molecule expression. But, in line of its much higher levels of secretion, TNFβ, rather than TNFα, was likely to play a preponderant role in AML blast differentiation. Moreover TNFβ and IFNγ were also likely to be involved in the AML blast differentiation-mediated by HLA-identical donor T-cell alloresponse against recipient AML blasts. In conclusion, we show herein that upon allogeneic reaction, TNFβ secretion contributes, in concert with IFNγ, to increase or restore surface molecules involved in AML blast interaction with T cells.

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Acknowledgements

This work was performed with the help of the Belgian Federal Services for Scientific Technical and Cultural Affairs and the Actions de recherches concertées, Communauté Française de Belgique, Direction de la Recherche Scientifique, the Association for Resarch against Cancer, and the Etablissement Français des Greffes. We wish to thank Professor Elizabeth Simpson for her very helpful comments on this paper. No conflicts of interest is present in this paper.

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Authors and Affiliations

  1. Cell Therapy Research Department, EFS-Rhone-Alpes, Lyon, France

    A Eljaafari, A Voisin & A Farre

  2. Immunogenetis Unit, HCL/BioMerieux, Hopital E. Herriot, Lyon, France

    A Eljaafari

  3. Ludwig Institute for Cancer Research and Experimental Medicine Unit, Catholic University of Louvin, Brussels, Belgium

    J Van Snick & F Cormont

  4. Immunology Department, CHLS, Lyon, France

    J Bienvenu

  5. Immunology Department, EFS-Rhone-Alpes, Lyon, France

    J Bernaud & D Rigal

  6. Hematology Department, Hopital E. Herriot, Lyon, France

    X Thomas

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Correspondence to A Eljaafari.

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Eljaafari, A., Van Snick, J., Voisin, A. et al. Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in acute myelogenous leukemia blasts, through secretion of inflammatory cytokines: dominant role for TNFβ, in concert with IFNγ. Leukemia 20, 1992–2001 (2006). https://doi.org/10.1038/sj.leu.2404375

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