Despite the fact that CD4+CD25+Foxp3+ regulatory T cells (Treg cells) play a central role in maintaining self-tolerance and that IL-17-producing CD4+ T cells (Th17 cells) are pathogenic in many autoimmune diseases, evidence to date has indicated that Th17 cells are resistant to suppression by human Foxp3+ Treg cells. It was recently demonstrated that CD39, an ectonucleotidase which hydrolyzes ATP, is expressed on a subset of human natural Treg cells. We found that although both CD4+CD25highCD39+ and CD4+CD25highCD39− T cells suppressed proliferation and IFN-γ production by responder T cells, only the CD4+CD25highCD39+, which were predominantly FoxP3+, suppressed IL-17 production, whereas CD4+CD25highCD39− T cells produced IL-17. An examination of T cells from multiple sclerosis patients revealed a normal frequency of CD4+CD25+CD127lowFoxP3+, but interestingly a deficit in the relative frequency and the suppressive function of CD4+CD25+CD127lowFoxP3+CD39+ Treg cells. The mechanism of suppression by CD39+ Treg cells appears to require cell contact and can be duplicated by adenosine, which is produced from ATP by the ectonucleotidases CD39 and CD73. Our findings suggest that CD4+CD25+Foxp3+CD39+ Treg cells play an important role in constraining pathogenic Th17 cells and their reduction in multiple sclerosis patients might lead to an inability to control IL-17 mediated autoimmune inflammation.

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The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

BackgroundThe relationship between prevalence of multiple sclerosis (MS) and latitude may be due to both genetic and environmental factors. The hypothesis that, in Ireland, MS prevalence is increasing and that northesouth differences relate to variation in serum 25-hydroxyvitamin D (25(OH)D) levels was tested in this study.