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

Son Nguyen, Claire Deleage, Samuel Darko, Amy Ransier, Duc P. Truong, Divyansh Agarwal, Alberto Sada Japp, Vincent H. Wu, Leticia Kuri-Cervantes, Mohamed Abdel-Mohsen, Perla M. Del Rio Estrada, Yuria Ablanedo-Terrazas, Emma Gostick, James A. Hoxie, Nancy R. Zhang, Ali Naji, Gustavo Reyes-Terán, Jacob D. Estes, David A. Price, Daniel C. DouekSteven G. Deeks, Marcus Buggert, Michael R. Betts

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Article numbereaax4077
JournalScience translational medicine
Volume11
Issue number523
DOIs
StatePublished - Dec 18 2019

ASJC Scopus subject areas

  • Medicine(all)

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    Nguyen, S., Deleage, C., Darko, S., Ransier, A., Truong, D. P., Agarwal, D., Japp, A. S., Wu, V. H., Kuri-Cervantes, L., Abdel-Mohsen, M., Del Rio Estrada, P. M., Ablanedo-Terrazas, Y., Gostick, E., Hoxie, J. A., Zhang, N. R., Naji, A., Reyes-Terán, G., Estes, J. D., Price, D. A., ... Betts, M. 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]. https://doi.org/10.1126/scitranslmed.aax4077