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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., 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: 01 Jul 2020 12:09
URI: http://orca-mwe.cf.ac.uk/id/eprint/128698

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