HIV Controllers Exhibit Effective CD8+ T Cell Recognition of HIV-1-Infected Non-activated CD4+ T Cells
| Autor: | Pedro Lamothe-Molina, Yovana Pacheco, Julie Boucau, Sylvie Le Gall, R. Brad Jones, Bruce D. Walker, Blandine Monel, Priya Jani, Annemarie McKeon |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Cytokine production Immunological synapse Virus entry 0302 clinical medicine Fluorescence resonance energy transfer Cytotoxic T cell Flow cytometry CD8+ T lymphocyte lcsh:QH301-705.5 Priority journal Fluorescence microscopy biology HIV cure Degranulation Virus particle virus diseases Synapse 3. Good health HLA Cytokine Protein cleavage Colorimetry Molecular recognition Human Antigen presentation Article General Biochemistry Genetics and Molecular Biology Virus 03 medical and health sciences Immune system Long terminal repeat Viral entry medicine Immune response Virus genome Granzyme CD4+ T lymphocyte Immunologic synapse Perforin HIV Human immunodeficiency virus 1 infection Virology Reverse transcriptase Cytotoxic T lymphocytes Elite controllers 030104 developmental biology Human cell lcsh:Biology (General) Immunology Protein protein interaction biology.protein T lymphocyte receptor Controlled study 030217 neurology & neurosurgery CD8 |
| Zdroj: | Cell Reports, Vol 27, Iss 1, Pp 142-153.e4 (2019) Repositorio EdocUR-U. Rosario Universidad del Rosario instacron:Universidad del Rosario |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.03.016 |
| Popis: | Summary: 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. Keywords: HIV cure, cytotoxic T lymphocytes, HLA, elite controllers, HIV, perforin, granzyme, immunologic synapse |
| Databáze: | OpenAIRE |
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