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PLoS Pathog. 2017 Jul 14;13(7):e1006489. doi: 10.1371/journal.ppat.1006489. eCollection 2017 Jul.

Negative modulation of suppressive HIV-specific regulatory T cells by IL-2 adjuvanted therapeutic vaccine.

Brezar V1,2,3, Hani L1,2,3, Surenaud M1,2,3, Hubert A1,2,3, Lacabaratz C1,2,3, Lelièvre JD1,2,3,4, Levy Y1,2,3,4, Seddiki N1,2,3.

Author information

1
Inserm, U955, Equipe 16, Créteil, Paris, France.
2
Université Paris Est, Faculté de médecine, Créteil, Paris, France.
3
Vaccine Research Institute (VRI), Créteil, Paris, France.
4
AP-HP, Hôpital H. Mondor - A. Chenevier, Service d'immunologie clinique et maladies infectieuses, Créteil, Paris, France.

Abstract

The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40. IL-2 administration increased significantly HIV-specific CD4+CD25+CD134+ T-cell responses, which inversely correlated with viral load after TI (r = -0.7, p <0.007) in the vaccine/IL-2 group. IL-2 increased global CD25+CD127lowFoxP3+Tregs (p <0.05) while it decreased HIV- but not CMV- specific CD39+FoxP3+CD25+CD134+Tregs (p <0.05). HIV-specific Tregs were inversely correlated with IFN-γ producing specific-effectors (p = 0.03) and positively correlated with viral load (r = 0.7, p = 0.01), revealing their undesired presence during chronic infection. Global Tregs, but not HIV-specific Tregs, inversely correlated with a decrease in exhausted PD1+CD95+ T-cells (p = 0.001). Altogether, our results underline the negative impact of HIV-specific Tregs on HIV-specific effectors and reveal the beneficial use of IL-2 as an adjuvant as its administration increases global Tregs that impact on T-cell exhaustion and decreases HIV-specific CD39+Tregs by shifting the balance towards effectors.

PMID:
28708863
PMCID:
PMC5529021
DOI:
10.1371/journal.ppat.1006489
[Indexed for MEDLINE]
Free PMC Article

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