Differential susceptibility to apoptosis of CD4+T cells expressing CCR5 and CXCR3 in patients with MS.
We aimed to evaluate differences in the susceptibility to apoptosis of CD4+CCR5+ and CD4+CXCR3+T cells between MS patients (N=41) and controls (N=15) 6 days after activation of peripheral blood cells with anti-CD3 antibodies and 24 h following stimulation with anti-Fas antibodies. Susceptibility to anti-CD3 induced activation-induced cell death (AICD) and Fas-mediated apoptosis was selectively increased in CD4+CCR5+T cells compared with CD4+CCR5- and CD4+CXCR3-/+T cells. Compared with controls, CD4+CCR5+T cells from patients with primary progressive MS (PPMS) were more resistant to anti-CD3-induced AICD and anti-Fas-induced apoptosis determined with the mitochondrial probe DiOC(6) (3-3'-dihexyloxacarboyanine iodide). Our findings point to a differential regulation in the susceptibility to apoptosis of CD4+T cells expressing CCR5 and CXCR3 and suggest an impairment in the mitochondria-mediated apoptotic deletion of CD4+CCR5+T cells in PPMS patients that may lead to their chronic persistence in peripheral blood from these patients.
Julià
Eva
E
Centre d'Esclerosi Múltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d'Hebron (HUVH)- Universitat Autònoma de Barcelona, Barcelona, Spain.
Edo
Mari Carmen
MC
Horga
Alex
A
Montalban
Xavier
X
Comabella
Manuel
M
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002232:Carbocyanines / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000276:immunology; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000276:immunology*; D018709:Statistics, Nonparametric; D019014:fas Receptor / Q000276:immunology
C515187:CXCR3 protein, human; D002232:Carbocyanines; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019014:fas Receptor; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine