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. (C) 2009 Elsevier Inc. All rights reserved.