Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in acute myelogenous leukemia blasts, through secretion of inflammatory cytokines: Dominant role for TNFbeta, in concert with IFNgamma.

Eljaafari, A;Van Snick, Jacques;Voisin, A;Cormont, F.;Thomas, X;et.al.
(2006) Leukemia — Vol. 20, n° 11, p. 1992-2001 (2006)

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Authors
  • Eljaafari, A
    Author
  • Van Snick, Jacquesorcid-logoUCLouvain
    Author
  • Voisin, A
    Author
  • Cormont, F.UCLouvain
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  • Thomas, X
    Author
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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 IFNgamma in the increase of HLA-class I and class II molecule expression. But, in line of its much higher levels of secretion, TNFbeta, rather than TNFalpha, was likely to play a preponderant role in AML blast differentiation. Moreover TNFbeta and IFNgamma 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, TNFbeta secretion contributes, in concert with IFNgamma, to increase or restore surface molecules involved in AML blast interaction with T cells.
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Eljaafari, A., Van Snick, J., Voisin, A., Cormont, F., Farre, A., Bienvenu, J., Bernaud, J., Rigal, D., & Thomas, X. (2006). Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in acute myelogenous leukemia blasts, through secretion of inflammatory cytokines: Dominant role for TNFbeta, in concert with IFNgamma. Leukemia, 20(11), 1992-2001. https://doi.org/10.1038/sj.leu.2404375 (Original work published 2006)