Abstract
Abstract Background: CD39 is an immune cell phenotype marker that exhibits ectonucleotidase activity, converting extracellular nucleotides to nucleosides. Although CD39 has been associated with Treg, the ectoenzyme is also expressed by a subpopulation of memory T-cells (CD4mem) with effector functions. We postulate that CD39 imparts plasticity to T helper type 17 (Th17) as well as co-ordinating Treg cellular programs of differentiation. Methods and Results: CD4mem cells were exposed to 1) IL6+IL1β+rTGFβ or 2) IL6+IL1β+IL23 or 3) IL6+IL1β+rTGFβ+IL23 to induce Th17 polarization. Cells were then treated with high dose IL2+anti-CD3/anti-CD28 to favour Treg differentiation and then re-exposed to Th17 differentiating conditions to induce putative reverse or suppressive Th17 (revTh17) cell. Impacts of purinergic mediators on the effector phenotype and functions were assessed. CD4mem could be differentiated sequentially to Th17, Treg and revTh17. In contrast to the inflammatory properties associated with prototypic Th17 cells, revTh17 exhibited a suppressive phenotype. Cells responded in a context-dependent manner to adenosine that boosted revTh17 suppression in the absence of TGFβ. Conclusion: Differential levels of expression of CD39 designate early Th17 cells from later Treg/revTh17 cell plasticity. The potential for Treg to revert to the inflammatory Th17 phenotype is mitigated by expression of CD39, as indicated by enhancements of suppressive function in vitro.
Published Version
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