1. Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells
- Author
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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
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Genetics ,Vaccine Related ,Immunization ,Sexually Transmitted Infections ,HIV/AIDS ,Prevention ,Clinical Research ,Infectious Diseases ,Vaccine Related (AIDS) ,1.1 Normal biological development and functioning ,Underpinning research ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,HIV Infections ,HIV-1 ,Humans ,Lymphoid Tissue ,Viral Load ,Biological Sciences ,Medical and Health Sciences ,Medical biotechnology ,Biomedical engineering - 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.
- Published
- 2019