Similar sensitivity of regulatory T cells towards CD95L-mediated apoptosis in patients with multiple sclerosis and healthy individuals.
Impaired suppressive function of CD4(+)CD25(high) regulatory T cells (T(reg)) has been reported as a novel pathogenetic mechanism in Multiple sclerosis (MS). We addressed if high apoptosis sensitivity of MS-T(reg) could explain this functional T(reg) defect. T(reg) from treatment-naïve MS patients showed high sensitivity towards CD95Ligand-mediated apoptosis and exhibited enhanced cell death to IL-2 and TCR-signal deprivation. Since susceptibility of T(reg) to cell death was similar in MS patients and healthy controls, this cannot explain the inhibitory dysfunction of T(reg) associated with MS. Furthermore, as cell death is not enhanced, therapeutic expansion of MS-T(reg)in vitro should be a reasonable and novel therapeutic option.
Fritzsching
Benedikt
B
Tumor Immunology Program D030, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. benedikt.fritzsching@dkfz.de
Korporal
Mirjam
M
Haas
Jürgen
J
Krammer
Peter H
PH
Suri-Payer
Elisabeth
E
Wildemann
Brigitte
B
D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016022:Case-Control Studies; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor