CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis.
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2009Citation:
Fletcher JM, Lonergan R, Costelloe L, Kinsella K, Moran B, O'Farrelly C, Tubridy N, Mills KH, CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis., Journal of Immunology, 183, 11, 2009, 7602-7610Download Item:
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Abstract:
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 hydrolyses ATP, is expressed on a subset of human natural Treg cells.
We found that although both CD4+CD25hiCD39+ and CD4+CD25hiCD39- T cells suppressed
proliferation and IFN-g production by responder T cells, only the CD4+CD25hiCD39+, which
were predominantly FoxP3+, suppressed IL-17 production, whereas CD4+CD25hiCD39- T cells
produced IL-17. An examination of T cells from multiple sclerosis (MS) patients revealed a
normal frequency of CD4+CD25+CD127loFoxP3+, but interestingly a deficit in the relative
frequency and the suppressive function of CD4+CD25+CD127loFoxP3+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 MS patients might lead to an inability
to control IL-17 mediated autoimmune inflammation.
Sponsor
Grant Number
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/millskhttp://people.tcd.ie/ofarrecl
http://people.tcd.ie/fletchj
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PUBLISHEDType of material:
Journal ArticleCollections:
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Journal of Immunology183
11
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Full text availableKeywords:
Immunology, T cells (Treg cells), CD39+Foxp3+Subject (TCD):
Immunology, Inflammation & Infection , NeuroscienceDOI:
http://dx.doi.org/10.4049/jimmunol.0901881ISSN:
0022-1767Licences: