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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

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  • Edda Blümel
  • Andreas Willerslev-Olsen
  • Maria Gluud
  • Lise M Lindahl
  • Simon Fredholm
  • Claudia Nastasi
  • Thorbjørn Krejsgaard
  • Bas G J Surewaard
  • Sergei B Koralov
  • Tengpeng Hu
  • Jenny L Persson
  • Charlotte Menné Bonefeld
  • Carsten Geisler
  • Lars Iversen
  • Jürgen C Becker
  • Mads Hald Andersen
  • Anders Woetmann
  • Terkild Brink Buus
  • Niels Ødum
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Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.

Original languageEnglish
Article numbere1641387
JournalOncoImmunology
Volume8
Issue number11
Pages (from-to)e1641387
ISSN2162-4011
DOIs
Publication statusPublished - 2019

    Research areas

  • alpha-toxin, Cutaneous T-cell lymphoma, disintegrin and metalloproteinase domain-containing protein 10, Staphylococcus aureus

ID: 58521792