HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells

Blandine Monel, Annmarie McKeon, Pedro Lamothe-Molina, Priya Jani, Julie Boucau, Yovana Pacheco, R. Brad Jones, Sylvie Le Gall, Bruce D. Walker

Resultado de la investigación: Contribución a RevistaArtículo

Resumen

Even with sustained antiretroviral therapy, resting CD4 + T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8 + T cells recognize infected, non-activated CD4 + T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8 + T cells from HIV controllers mediate more effective immune recognition than CD8 + T cells from progressors. These results indicate that non-activated HIV-infected CD4 + T cells can be targeted by CD8 + T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir. The cure for HIV is not achievable due to HIV reservoirs, mostly in resting CD4 + T cells. Monel et al. show that CD8 + T cells from HIV controllers are able to establish immunological synapses with HIV + resting CD4 + T cells, leading to IFN-γ, MIP1-β production, degranulation, and the elimination of the target cells.

Idioma originalEnglish (US)
Páginas (desde-hasta)142-153.e4
PublicaciónCell Reports
Volumen27
N.º1
DOI
EstadoPublished - abr 2 2019
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Citar esto

Monel, B., McKeon, A., Lamothe-Molina, P., Jani, P., Boucau, J., Pacheco, Y., ... Walker, B. D. (2019). HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells. Cell Reports, 27(1), 142-153.e4. https://doi.org/10.1016/j.celrep.2019.03.016
Monel, Blandine ; McKeon, Annmarie ; Lamothe-Molina, Pedro ; Jani, Priya ; Boucau, Julie ; Pacheco, Yovana ; Jones, R. Brad ; Le Gall, Sylvie ; Walker, Bruce D. / HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells. En: Cell Reports. 2019 ; Vol. 27, N.º 1. pp. 142-153.e4.
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abstract = "Even with sustained antiretroviral therapy, resting CD4 + T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8 + T cells recognize infected, non-activated CD4 + T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8 + T cells from HIV controllers mediate more effective immune recognition than CD8 + T cells from progressors. These results indicate that non-activated HIV-infected CD4 + T cells can be targeted by CD8 + T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir. The cure for HIV is not achievable due to HIV reservoirs, mostly in resting CD4 + T cells. Monel et al. show that CD8 + T cells from HIV controllers are able to establish immunological synapses with HIV + resting CD4 + T cells, leading to IFN-γ, MIP1-β production, degranulation, and the elimination of the target cells.",
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Monel, B, McKeon, A, Lamothe-Molina, P, Jani, P, Boucau, J, Pacheco, Y, Jones, RB, Le Gall, S & Walker, BD 2019, 'HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells', Cell Reports, vol. 27, n.º 1, pp. 142-153.e4. https://doi.org/10.1016/j.celrep.2019.03.016

HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells. / Monel, Blandine; McKeon, Annmarie; Lamothe-Molina, Pedro; Jani, Priya; Boucau, Julie; Pacheco, Yovana; Jones, R. Brad; Le Gall, Sylvie; Walker, Bruce D.

En: Cell Reports, Vol. 27, N.º 1, 02.04.2019, p. 142-153.e4.

Resultado de la investigación: Contribución a RevistaArtículo

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T1 - HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells

AU - Monel, Blandine

AU - McKeon, Annmarie

AU - Lamothe-Molina, Pedro

AU - Jani, Priya

AU - Boucau, Julie

AU - Pacheco, Yovana

AU - Jones, R. Brad

AU - Le Gall, Sylvie

AU - Walker, Bruce D.

PY - 2019/4/2

Y1 - 2019/4/2

N2 - Even with sustained antiretroviral therapy, resting CD4 + T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8 + T cells recognize infected, non-activated CD4 + T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8 + T cells from HIV controllers mediate more effective immune recognition than CD8 + T cells from progressors. These results indicate that non-activated HIV-infected CD4 + T cells can be targeted by CD8 + T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir. The cure for HIV is not achievable due to HIV reservoirs, mostly in resting CD4 + T cells. Monel et al. show that CD8 + T cells from HIV controllers are able to establish immunological synapses with HIV + resting CD4 + T cells, leading to IFN-γ, MIP1-β production, degranulation, and the elimination of the target cells.

AB - Even with sustained antiretroviral therapy, resting CD4 + T cells remain a persistent reservoir of HIV infection, representing a critical barrier to curing HIV. Here, we demonstrate that CD8 + T cells recognize infected, non-activated CD4 + T cells in the absence of de novo protein production, as measured by immune synapse formation, degranulation, cytokine production, and killing of infected cells. Immune recognition is induced by HLA-I presentation of peptides derived from incoming viral particles, and recognition occurred either following cell-free virus infection or following cell-to-cell spread. CD8 + T cells from HIV controllers mediate more effective immune recognition than CD8 + T cells from progressors. These results indicate that non-activated HIV-infected CD4 + T cells can be targeted by CD8 + T cells directly after HIV entry, before reverse transcription, and thus before the establishment of latency, and suggest a mechanism whereby the immune response may reduce the size of the HIV reservoir. The cure for HIV is not achievable due to HIV reservoirs, mostly in resting CD4 + T cells. Monel et al. show that CD8 + T cells from HIV controllers are able to establish immunological synapses with HIV + resting CD4 + T cells, leading to IFN-γ, MIP1-β production, degranulation, and the elimination of the target cells.

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Monel B, McKeon A, Lamothe-Molina P, Jani P, Boucau J, Pacheco Y y otros. HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells. Cell Reports. 2019 abr 2;27(1):142-153.e4. https://doi.org/10.1016/j.celrep.2019.03.016