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Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+T cells in cutaneous T-cell lymphoma
- Source :
- OncoImmunology; November 2019, Vol. 8 Issue: 11
- Publication Year :
- 2019
-
Abstract
- ABSTRACTStaphylococcus aureusis 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 aureusderived 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.
Details
- Language :
- English
- ISSN :
- 21624011 and 2162402X
- Volume :
- 8
- Issue :
- 11
- Database :
- Supplemental Index
- Journal :
- OncoImmunology
- Publication Type :
- Periodical
- Accession number :
- ejs51002792
- Full Text :
- https://doi.org/10.1080/2162402X.2019.1641387