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S100A9 Tetramers, Which are Ligands of CD85j, Increase the Ability of MVAHIV-Primed NK Cells to Control HIV Infection.

Moreno-Nieves UY, Didier C, Lévy Y, Barré-Sinoussi F, Scott-Algara D, ANRS HIV Vaccine Network (AHV - Front Immunol (2015)

Bottom Line: Natural killer (NK) cells are the major antiviral effector population of the innate immune system.We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells.We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells.

View Article: PubMed Central - PubMed

Affiliation: Unité de Régulation des Infections Rétrovirales, Department of Virology, Institut Pasteur , Paris , France.

ABSTRACT
Natural killer (NK) cells are the major antiviral effector population of the innate immune system. We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine candidate, MVAHIV, prime NK cells to specifically control HIV infection in autologous CD4(+) T cells. In this study, we analyzed whether stimulation of NK cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates the subsequent anti-HIV activity of NK cells. We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells. Interestingly, we observed that stimulation of NK cells by S100A9 tetramers, prior to the priming, significantly increased the subsequent anti-HIV activity of NK cells and that the enhanced anti-HIV activity was observed following different conditions of priming, including the MVAHIV-priming. As S100A9 tetramers alone directly increase the anti-HIV activity of NK cells and as this increased anti-HIV activity is also observed following the interaction of NK cells with MVAHIV-infected DCs, we propose S100A9 tetramers as potential adjuvants to stimulate the anti-HIV activity of NK cells.

No MeSH data available.


Related in: MedlinePlus

S100A9-tetramer stimulation and MVAHIV-priming significantly enhance by ability of NK cells to control HIV infection. S100A9-stimulated NK cells were tested in their ability to control HIV infection in autologous CD4+ T cells. (A) NK cells were stimulated or not by S100A9 tetramers or monomers at 1 μg/ml during 4 h and cultured with HIV-infected CD4+ T cells, and after 10 days of culture, the percentage of intracellular HIV-1 p24+ CD4+ T cells was analyzed by flow cytometry; graph shows cumulative results from six independent experiments. (B) Schema depicts the protocol used in (C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the ability of NK cells to control HIV infection was assessed at 10 days post-HIV infection. (C) Graph shows the percentage of HIV p24+ CD4+ T cells in culture; cumulative results from eight independent experiments are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
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Figure 4: S100A9-tetramer stimulation and MVAHIV-priming significantly enhance by ability of NK cells to control HIV infection. S100A9-stimulated NK cells were tested in their ability to control HIV infection in autologous CD4+ T cells. (A) NK cells were stimulated or not by S100A9 tetramers or monomers at 1 μg/ml during 4 h and cultured with HIV-infected CD4+ T cells, and after 10 days of culture, the percentage of intracellular HIV-1 p24+ CD4+ T cells was analyzed by flow cytometry; graph shows cumulative results from six independent experiments. (B) Schema depicts the protocol used in (C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the ability of NK cells to control HIV infection was assessed at 10 days post-HIV infection. (C) Graph shows the percentage of HIV p24+ CD4+ T cells in culture; cumulative results from eight independent experiments are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.

Mentions: Then, we sought to determine the capacity of NK cells to control HIV infection in CD4+ T cells after stimulation by S100A9 tetramers and priming by DCs (Figure 4). We assessed the ability of NK cells to control HIV infection in CD4+ T cells by analyzing the percentage of HIV-1 p24-positive (HIV p24+) CD4+ T cells in culture with primed NK cells, at day 10 post HIV infection. As previously described (10), we found that stimulation of NK cells by S100A9 tetramers, but not S100A9 monomers, enhanced the capacity of NK cells to control HIV infection (Figure 4A).


S100A9 Tetramers, Which are Ligands of CD85j, Increase the Ability of MVAHIV-Primed NK Cells to Control HIV Infection.

Moreno-Nieves UY, Didier C, Lévy Y, Barré-Sinoussi F, Scott-Algara D, ANRS HIV Vaccine Network (AHV - Front Immunol (2015)

S100A9-tetramer stimulation and MVAHIV-priming significantly enhance by ability of NK cells to control HIV infection. S100A9-stimulated NK cells were tested in their ability to control HIV infection in autologous CD4+ T cells. (A) NK cells were stimulated or not by S100A9 tetramers or monomers at 1 μg/ml during 4 h and cultured with HIV-infected CD4+ T cells, and after 10 days of culture, the percentage of intracellular HIV-1 p24+ CD4+ T cells was analyzed by flow cytometry; graph shows cumulative results from six independent experiments. (B) Schema depicts the protocol used in (C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the ability of NK cells to control HIV infection was assessed at 10 days post-HIV infection. (C) Graph shows the percentage of HIV p24+ CD4+ T cells in culture; cumulative results from eight independent experiments are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
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Figure 4: S100A9-tetramer stimulation and MVAHIV-priming significantly enhance by ability of NK cells to control HIV infection. S100A9-stimulated NK cells were tested in their ability to control HIV infection in autologous CD4+ T cells. (A) NK cells were stimulated or not by S100A9 tetramers or monomers at 1 μg/ml during 4 h and cultured with HIV-infected CD4+ T cells, and after 10 days of culture, the percentage of intracellular HIV-1 p24+ CD4+ T cells was analyzed by flow cytometry; graph shows cumulative results from six independent experiments. (B) Schema depicts the protocol used in (C), in brief: DCs were infected or not by MVAWT or MVAHIV, and 24 h later non-infected DCs and S100A9-stimulated NK cells were added to the culture; and 96 h later (4 days) NK cells were transferred to a culture of HIV-infected CD4+ T cells and the ability of NK cells to control HIV infection was assessed at 10 days post-HIV infection. (C) Graph shows the percentage of HIV p24+ CD4+ T cells in culture; cumulative results from eight independent experiments are expressed as mean ± SE and p values are shown. A9M, S100A9 monomer; A9T, S100A9 tetramer; DC-MVAWT, MVAWT-infected DC; DC-MVAHIV, MVAHIV-infected DC.
Mentions: Then, we sought to determine the capacity of NK cells to control HIV infection in CD4+ T cells after stimulation by S100A9 tetramers and priming by DCs (Figure 4). We assessed the ability of NK cells to control HIV infection in CD4+ T cells by analyzing the percentage of HIV-1 p24-positive (HIV p24+) CD4+ T cells in culture with primed NK cells, at day 10 post HIV infection. As previously described (10), we found that stimulation of NK cells by S100A9 tetramers, but not S100A9 monomers, enhanced the capacity of NK cells to control HIV infection (Figure 4A).

Bottom Line: Natural killer (NK) cells are the major antiviral effector population of the innate immune system.We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells.We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells.

View Article: PubMed Central - PubMed

Affiliation: Unité de Régulation des Infections Rétrovirales, Department of Virology, Institut Pasteur , Paris , France.

ABSTRACT
Natural killer (NK) cells are the major antiviral effector population of the innate immune system. We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine candidate, MVAHIV, prime NK cells to specifically control HIV infection in autologous CD4(+) T cells. In this study, we analyzed whether stimulation of NK cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates the subsequent anti-HIV activity of NK cells. We found that S100A9 tetramers activate NK cells and that DCs enhance the anti-HIV activity of NK cells. Interestingly, we observed that stimulation of NK cells by S100A9 tetramers, prior to the priming, significantly increased the subsequent anti-HIV activity of NK cells and that the enhanced anti-HIV activity was observed following different conditions of priming, including the MVAHIV-priming. As S100A9 tetramers alone directly increase the anti-HIV activity of NK cells and as this increased anti-HIV activity is also observed following the interaction of NK cells with MVAHIV-infected DCs, we propose S100A9 tetramers as potential adjuvants to stimulate the anti-HIV activity of NK cells.

No MeSH data available.


Related in: MedlinePlus