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 me...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | Colombia |
| Institución: | Universidad del Rosario |
| Repositorio: | Repositorio EdocUR - U. Rosario |
| Idioma: | inglés |
| OAI Identifier: | oai:repository.urosario.edu.co:10336/23642 |
| Acceso en línea: | https://doi.org/10.1016/j.celrep.2019.03.016 https://repository.urosario.edu.co/handle/10336/23642 |
| Access Level: | acceso abierto |
| Palabra clave: | T lymphocyte receptor Antigen presentation Article CD4+ T lymphocyte CD8+ T lymphocyte Colorimetry Controlled study Cytokine production Degranulation Flow cytometry Fluorescence microscopy Fluorescence resonance energy transfer Human Human cell Human immunodeficiency virus 1 infection Immune response Immunological synapse Long terminal repeat Molecular recognition Priority journal Protein cleavage Protein protein interaction Synapse Virus entry Virus genome Virus particle Cytotoxic T lymphocytes Elite controllers Granzyme HIV HIV cure HLA Immunologic synapse Perforin |
| 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. 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-?, MIP1-? production, degranulation, and the elimination of the target cells. © 2019 The Authors |
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