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

S Nguyen, C Deleage, S Darko, A Ransier… - Science translational …, 2019 - science.org
S Nguyen, C Deleage, S Darko, A Ransier, DP Truong, D Agarwal, AS Japp, VH Wu
Science translational medicine, 2019science.org
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 …
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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