{"doi":"10.1172/jci155251","title":"Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy","abstract":"Interleukin-10 (IL-10) is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper (Tfh) cell differentiation and germinal center formation. In SIV-infected macaques, levels of IL-10 in plasma and lymph nodes (LNs) were induced by infection and not normalized with antiretroviral therapy (ART). During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including Tfh cells, and predicted the frequency of CD4+ Tfh cells and their cell-associated SIV-DNA content during ART, respectively. In ART-treated rhesus macaques, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B cell follicle in proximity to IL-10. Finally, we demonstrated that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques reduced B cell follicle maintenance and, by extension, LN memory CD4+ T cells, including Tfh cells and those expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.","journal":"Journal of Clinical Investigation","year":2022,"id":239683,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244982,"name":"Susan Pereira Ribeiro","orcid":"0000-0002-3127-3138","position":1,"is_corresponding":false},{"id":95224,"name":"Chi Ngai Chan","orcid":"0000-0001-9106-9481","position":2,"is_corresponding":false},{"id":242324,"name":"Malika Aïd","orcid":"0000-0002-4498-7893","position":3,"is_corresponding":false},{"id":412158,"name":"Claire Deléage","orcid":"0000-0002-3507-0055","position":4,"is_corresponding":false},{"id":278235,"name":"Luca Micci","orcid":"0000-0003-1980-4271","position":5,"is_corresponding":false},{"id":242326,"name":"María Pino","orcid":"0000-0003-4954-5215","position":6,"is_corresponding":false},{"id":248739,"name":"Barbara Cervasi","orcid":null,"position":7,"is_corresponding":false},{"id":866699,"name":"Gopalan Raghunathan","orcid":null,"position":8,"is_corresponding":false},{"id":866700,"name":"Eric Rimmer","orcid":null,"position":9,"is_corresponding":false},{"id":866701,"name":"Gulesi Ayanoglu","orcid":null,"position":10,"is_corresponding":false},{"id":450742,"name":"Guoxin Wu","orcid":"0009-0008-8449-8155","position":11,"is_corresponding":false},{"id":400085,"name":"Neeta Shenvi","orcid":"0000-0003-0149-8384","position":12,"is_corresponding":false},{"id":866702,"name":"Richard J.O. 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