TY - JOUR
T1 - Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells
AU - Nguyen, Son
AU - Deleage, Claire
AU - Darko, Samuel
AU - Ransier, Amy
AU - Truong, Duc P.
AU - Agarwal, Divyansh
AU - Japp, Alberto Sada
AU - Wu, Vincent H.
AU - Kuri-Cervantes, Leticia
AU - Abdel-Mohsen, Mohamed
AU - Del Rio Estrada, Perla M.
AU - Ablanedo-Terrazas, Yuria
AU - Gostick, Emma
AU - Hoxie, James A.
AU - Zhang, Nancy R.
AU - Naji, Ali
AU - Reyes-Terán, Gustavo
AU - Estes, Jacob D.
AU - Price, David A.
AU - Douek, Daniel C.
AU - Deeks, Steven G.
AU - Buggert, Marcus
AU - Betts, Michael R.
N1 - Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
PY - 2019/12/18
Y1 - 2019/12/18
N2 - 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.
AB - 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.
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U2 - 10.1126/scitranslmed.aax4077
DO - 10.1126/scitranslmed.aax4077
M3 - Article
C2 - 31852798
AN - SCOPUS:85079527146
SN - 1946-6234
VL - 11
JO - Science translational medicine
JF - Science translational medicine
IS - 523
M1 - eaax4077
ER -