{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nguyen S"],"funding":["National Institutes of Health","Wellcome Trust","Division of Intramural Research, National Institute of Allergy and Infectious Diseases"],"pagination":["eaax4077"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7265335"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(523)"],"pubmed_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."],"journal":["Science translational medicine"],"pubmed_title":["Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells."],"pmcid":["PMC7265335"],"funding_grant_id":["AI 076066, AI 118694, and the BEAT-HIV Delaney Collaboratory AI 126620","P30 AI 027763","100326/Z/12/Z","P51OD011092","AI 129636"],"pubmed_authors":["Truong DP","Ablanedo-Terrazas Y","Abdel-Mohsen M","Nguyen S","Del Rio Estrada PM","Douek DC","Price DA","Hoxie JA","Darko S","Japp AS","Wu VH","Deleage C","Zhang NR","Reyes-Teran G","Naji A","Kuri-Cervantes L","Estes JD","Buggert M","Agarwal D","Betts MR","Ransier A","Gostick E","Deeks SG"],"additional_accession":[]},"is_claimable":false,"name":"Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells.","description":"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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Dec","modification":"2024-02-14T23:21:11.201Z","creation":"2020-06-07T07:16:35Z"},"accession":"S-EPMC7265335","cross_references":{"pubmed":["31852798"],"doi":["10.1126/scitranslmed.aax4077"]}}