Sequential expression of CD39 regulates late developmental T helper type 17 plasticity imparting a regulatory cell phenotype

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• 作者：Dr Maria Serena Longhi^a ; ^b ; ^{maria.longhi@kcl.ac.uk} ; Aiping Bai^b ; Yan Wu^b ; Terry B Strom^b ; Simon C Robson^b
• 刊名：The Lancet
• 出版年：2013
• 出版时间：27 February, 2013
• 年：2013
• 卷：381
• 期：supp_S1
• 页码：S65
• 全文大小：41 K

文摘

Background

CD39 is an immune cell phenotype marker that exhibits ectonucleotidase activity, converting extracellular nucleotides to nucleosides. Although CD39 has been associated with regulatory T cells (Treg), the ectoenzyme is also expressed by a subpopulation of memory T cells (CD4^mem) with effector functions. We postulate that CD39 imparts plasticity to effector T helper type 17 (Th17) as well as co-ordinating Treg cellular programmes of differentiation.

Methods

Experiments were performed with peripheral blood mononuclear cells obtained from healthy blood donors. Sorted CD4⁺CD45RO⁺ memory cells (CD4^mem) were exposed to interleukin (IL) 6 plus IL1¦Â plus recombinant transforming growth factor ¦Â1 (rTGF) or IL6 plus IL1¦Â plus IL23, or IL6 plus IL1¦Â plus rTGF ¦Â1 plus IL23 to induce Th17 polarisation. Cells at Th17 stage were then treated with high-dose IL2 plus anti-CD3/anti-CD28 to favour Treg differentiation and then re-exposed to Th17 differentiating conditions to induce putative reverse or suppressive Th17 (rev/regTh17) cell. Impacts of purinergic mediators on cell effector phenotype and functions were assessed.

Findings

CD4^mem could be differentiated sequentially to Th17, Treg, and rev/regTh17. In contrast to the inflammatory properties associated with prototypic Th17 cells, rev/regTh17 exhibited a suppressive phenotype (ie, CD39^high, CD73^high, FOXP3⁺) and were able to control CD4⁺CD25^? cell proliferation and pro-inflammatory cytokine (IFN¦Ã, IL17) production. rev/regTh17 did not upregulate CD39, CD73, and FOXP3 and did not undergo increase in their suppressive function after culture with adenosine.

Interpretation

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.

Funding

UK Medical Research Council.