Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
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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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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.
Originalsprog | Engelsk |
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Artikelnummer | e1641387 |
Tidsskrift | OncoImmunology |
Vol/bind | 8 |
Udgave nummer | 11 |
Antal sider | 7 |
ISSN | 2162-4011 |
DOI | |
Status | Udgivet - 2019 |
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