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 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

• Fecha de publicación: 2019
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• 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
• 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
• License: Abierto (Texto Completo)