Título:
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Antigen production after latency reversal and expression of inhibitory receptors in CD8+ T cells limit the killing of HIV-1 reactivated cells
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Autor/a:
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Ruiz, A.; Blanch-Lombarte, Oscar; Jimenez-Moyano, Esther; Ouchi, Dan; Mothe, Beatriz.; Peña, R.; Gálvez, Cristina; Genescà Ferrer, Meritxell.; Martínez Picado, Francisco Javier; Goulder, P.; Barnard, R.; Howell, B.; Pérez-Álvarez, Núria; Prado, Julia G..; Universitat Autònoma de Barcelona
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Abstract:
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The so-called shock and kill therapies aim to combine HIV-1 reactivation by latency-reversing agents (LRA) with immune clearance to purge the HIV-1 reservoir. The clinical use of LRA has demonstrated detectable perturbations in the HIV-1 reservoir without measurable reductions to date. Consequently, fundamental questions concerning the limitations of the recognition and killing of LRA-reactivated cells by effector cells such as CD8+ T cells remain to be answered. Here, we developed a novel experimental framework where we combine the use of cytotoxic CD8+ T-cell lines and ex vivo CD8+ T cells from HIV-1-infected individuals with functional assays of LRA-inducible reactivation to delineate immune barriers to clear the reservoir. Our results demonstrate the potential for early recognition and killing of reactivated cells by CD8+ T cells. However, the potency of LRAs when crossing the barrier for antigen presentation in target cells, together with the lack of expression of inhibitory receptors in CD8+ T cells, are critical events to maximize the speed of recognition and the magnitude of the killing of LRA-inducible provirus. Taken together, our findings highlight direct limitations in LRA potency and CD8+ T cell functional status to succeed in the cure of HIV-1 infection. |
Materia(s):
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-Human immunodeficiency virus -HIV-1 reservoir -HIV-1 immunogen -Shock and kill -CTL (Cytotoxic T lymphocyte) -Inhibitory receptors |
Derechos:
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open access
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Tipo de documento:
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Article |
Editor:
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Uri:
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https://ddd.uab.cat/record/223497
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