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

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...

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Detalles Bibliográficos
Autores principales: Monel, Blandine, McKeon, Annmarie, Lamothe-Molina, Pedro, Jani, Priya, Boucau, Julie, Pacheco, Yovana, Jones, R. Brad, Le Gall, Sylvie, Walker, Bruce D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449512/
https://www.ncbi.nlm.nih.gov/pubmed/30943397
http://dx.doi.org/10.1016/j.celrep.2019.03.016
Descripción
Sumario: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.