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

by Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki

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 +CD127^lowFoxP3⁺Tregs (p +FoxP3⁺CD25⁺CD134⁺Tregs (p +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.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2tUo4ZX
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