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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

IL-7 abrogates memory T regulatory cell functions by modulation of CD39/ATP axis in vitro and in vivo in HIV infected and non-infected patients

  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
  • 2,
  • 1 and
  • 1
Retrovirology20129 (Suppl 2) :P290

https://doi.org/10.1186/1742-4690-9-S2-P290

  • Published:

Keywords

  • Cell Response
  • Healthy Donor
  • Suppressive Effect
  • Cytokine Profile
  • Purinergic Receptor

Background

IL-7 cytokine regulate the expansion and maturation of T cells. The good safety profile of IL-7 raises the opportunity of its use as a vaccine adjuvant. However, its role on the regulation of T cell responses has not been explored. We investigated the effects of IL-7 on regulatory T cell (Treg) functions invitro and invivo.

Methods

Treg and CD8+ T cells were isolated from healthy donors (n=10) (HD) and chronically HAART treated HIV+ pt enrolled in a phase I/II IL-7 INSPIRE study (n=6X) (Levy et al, CID, in press). Treg subpopulations (naïve CD45RA+FoxP3++CD45RA+CD25++CD127+/-, memory (mTreg) Foxp3highCD45RA-CD25highCD127low, FoxP3++CD45RA-CD25++CD127+/-) were cultured with IL-7 (10 ng/ml). Phenotype (CD39, Bcl-2, Stat5P, purinergic receptor P2X7R), suppression of the proliferation of autologous antiCD3 activated CD8+ T cells (CFSE stained) and cytokine profile (IL-17 production) of Treg were analyzed.

Results

In HD, IL-7 induces expression of STAT5 and BCL-2 on all Treg populations. IL-7 reduces the suppressive effects of mTreg on CD8+ proliferation (% CFSE low w/wo IL7 was 15% and 40%, respectively, n=4, P=0.01). This effect was associated with a down-modulation of CD39 enzyme (MFI 65 vs 90 w/wo IL7, P=0.01) and an increase of P2X7R expression. IL-7 effect was reproduced using anti-CD39 blocking antibody and PPAD (inhibitor of P2X7R). IL-7 incubated Treg switched to a Th17 phenotype as assessed by the increase of Th17 production and RORgC expression. IL-7 treated patients exhibited a decrease of the frequency of Treg/CD39+ and an increase of RORgC mRNA in PBMCs as compared to pre-IL-7 therapy.

Conclusion

IL-7 relieves the suppressive effect of mTreg through a modulation of the CD39/ATP axis. By increasing P2X7R expression, IL-7 increases the susceptibility of these cells to ATP, a trigger of Th17 differentiation. An effect also observed in IL-7 treated patients. These results suggest that IL-7 could be used as adjuvant to reinforce T cell responses.

Authors’ Affiliations

(1)
Faculté de médecine, Université Paris-Est, Créteil, Créteil, France
(2)
Cytheris, France

Copyright

© Younas et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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