CD39+Foxp3+ regulatory T cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis

Fletcher J; Lonergan R; Costelloe L; Kinsella K; Moran B; O’Farrelly C; Tubridy N; Mills K

doi:10.4049/jimmunol.0901881

CD39+Foxp3+ regulatory T cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis

Fletcher J, Lonergan R, Costelloe L +5 more2009The Journal of ImmunologyJournal Article

10.4049/jimmunol.0901881 PubMed Free full text

Immune/InnateNeurological

Abstract

CD39Foxp3 Regulatory T Cells Suppress Pathogenic Th17 Cells and Are Impaired in Multiple Sclerosis1 Jean M. Fletcher,* Roisin Lonergan,† Lisa Costelloe,† Katie Kinsella,† Barry Moran,* Cliona O’Farrelly,* Niall Tubridy,† and Kingston H. G. Mills2* Despite the fact that CD4CD25Foxp3 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 CD4CD25highCD39 and CD4CD25highCD39 T cells suppressed proliferation and IFN- production by responder T cells, only the CD4CD25high CD39, which were predominantly FoxP3, suppressed IL-17 production, whereas CD4CD25highCD39 T cells produced IL-17. An examination of T cells from multiple sclerosis patients revealed a normal frequency of CD4CD25CD127lowFoxP3, but interestingly a deﬁcit in the relative frequency and the suppressive function of CD4CD25CD127lowFoxP3CD39 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 CD4CD25Foxp3CD39 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. The Journal of Immunology, 2009, 183: 7602–7610. I n healthy individuals naturally occurring Treg (nTreg)3 cells play an essential role in maintaining tolerance to self Ags and preventing autoimmune diseases. Multiple sclerosis (MS) is an autoimmune disease caused by pathogenic T cells speciﬁc for myelin- Ags in the CNS. T cell responses

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady

Key Biomarkers

AdenosineCD39+Foxp3+ regulatory T cellsCD4+CD25+CD127low Treg cellsCD73IL-17-producing Th17 cells

Symptom Clusters

Autoimmune inflammationImpaired regulatory T cell suppressionPathogenic Th17 cell activity

Cited By (6)

References (4)