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Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

Nguyen, Son, Deleage, Claire, Darko, Samuel, Ransier, Amy, Truong, Duc P., Agarwal, Divyansh, Japp, Alberto Sada, Wu, Vincent H., Kuri-Cervantes, Leticia, Abdel-Mohsen, Mohamed, Del Rio Estrada, Perla M., Ablanedo-Terrazas, Yuria, Gostick, Emma, Hoxie, James A., Zhang, Nancy R., Naji, Ali, Reyes-Terán, Gustavo, Estes, Jacob D., Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Douek, Daniel C., Deeks, Steven G., Buggert, Marcus and Betts, Michael R. 2019. Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells. Science Translational Medicine 11 (523) , eaax4077. 10.1126/scitranslmed.aax4077

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Abstract

The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell–associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Publisher: American Association for the Advancement of Science
ISSN: 1946-6234
Date of First Compliant Deposit: 17 January 2020
Date of Acceptance: 11 November 2019
Last Modified: 26 Nov 2022 14:51
URI: https://orca.cardiff.ac.uk/id/eprint/128698

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