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J Immunol. 2013 Sep 15;191(6):3161-8. doi: 10.4049/jimmunol.1203547. Epub 2013 Aug 21.

IL-7 modulates in vitro and in vivo human memory T regulatory cell functions through the CD39/ATP axis.

Author information

1
INSERM U955, Institut Mondor de Recherche Biomédicale, 94010 Créteil, France.

Abstract

The heterogeneity of human regulatory T cells (Tregs) may explain the discrepancies between studies on Tregs in physiology and pathology. Contrasting effects of IL-7 on the expansion and survival of human Tregs were reported. Therefore, we investigated the effects of IL-7 on the phenotype and function of well-characterized populations of human Tregs. We show that IL-7 signals via the CD127 receptor on naive, memory, and activated memory Tregs sorted from the blood of healthy donors, but it does not affect their proliferation. In contrast, IL-7 affects their suppressive capacities differently. This effect was modest on naive Tregs but was dramatic (90%) on memory Tregs. We provide evidence that IL-7 exerts a synergistic effect through downmodulation of the ectoenzyme CD39, which converts ATP to ADP/AMP, and an increase in ATP receptor P2X7. Both effects lead to an increase in the ATP-mediated effect, tipping the balance to favor Th17 conversion. Using an IL-7 therapeutic study, we show that IL-7 exerts the same effects in vitro and in vivo in HIV-infected individuals. Globally, our data show that IL-7 negatively regulates Tregs and contributes to increase the number of tools that may affect Treg function in pathology.

PMID:
23966629
DOI:
10.4049/jimmunol.1203547
[Indexed for MEDLINE]
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