Staphylococcal Alpha-toxin Tilts the Balance Between Malignant and Non-malignant CD4 T Cells in Cutaneous T-cell Lymphoma

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2019 Oct 25

PMID 31646088

Citations 20

Authors

Edda Blumel

Andreas Willerslev-Olsen

Maria Gluud

Lise M Lindahl

Simon Fredholm

Claudia Nastasi

Thorbjorn Krejsgaard

Bas G J Surewaard

Sergei B Koralov

Tengpeng Hu

Jenny L Persson

Charlotte Menne Bonefeld

Carsten Geisler

Lars Iversen

Jurgen C Becker

Mads Hald Andersen

Anders Woetmann

Terkild Brink Buus

Niels Odum

Affiliations

Soon will be listed here.

Abstract

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 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.

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