{"doi":"10.1371/journal.ppat.1009533","title":"T cell immune discriminants of HIV reservoir size in a pediatric cohort of perinatally infected individuals","abstract":"The size of the latent HIV reservoir is associated with the timing of therapeutic interventions and overall health of the immune system. Here, we demonstrate that T cell phenotypic signatures associate with viral reservoir size in a cohort of HIV vertically infected children and young adults under durable viral control, and who initiated anti-retroviral therapy (ART) <2 years old. Flow cytometry was used to measure expression of immune activation (IA), immune checkpoint (ICP) markers, and intracellular cytokine production after stimulation with GAG peptides in CD4 and CD8 T cells from cross-sectional peripheral blood samples. We also evaluated the expression of 96 genes in sort-purified total CD4 and CD8 T cells along with HIV-specific CD4 and CD8 T cells using a multiplexed RT-PCR approach. As a measure of HIV reservoir, total HIV-DNA quantification by real-time PCR was performed. Poisson regression modeling for predicting reservoir size using phenotypic markers revealed a signature that featured frequencies of PD-1+CD4 T cells, TIGIT+CD4 T cells and HIV-specific (CD40L+) CD4 T cells as important predictors and it also shows that time of ART initiation strongly affects their association with HIV-DNA. Further, gene expression analysis showed that the frequencies of PD-1+CD4 T cells associated with a CD4 T cell molecular profile skewed toward an exhausted Th1 profile. Our data provide a link between immune checkpoint molecules and HIV persistence in a pediatric cohort as has been demonstrated in adults. Frequencies of PD-1+ and TIGIT+CD4 T cells along with the frequency of HIV-specific CD4 T cells could be associated with the mechanism of viral persistence and may provide insight into potential targets for therapeutic intervention.","journal":"PLoS Pathogens","year":2021,"id":179392,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":382152,"name":"Lesley de Armas","orcid":null,"position":1,"is_corresponding":false},{"id":724406,"name":"Sara Domínguez‐Rodríguez","orcid":"0000-0003-3747-9265","position":2,"is_corresponding":false},{"id":380957,"name":"Suresh Pallikkuth","orcid":"0000-0003-4451-8859","position":3,"is_corresponding":false},{"id":726850,"name":"Vinh Dinh","orcid":"0000-0002-8148-8508","position":4,"is_corresponding":false},{"id":669906,"name":"Li Pan","orcid":"0000-0002-3388-5509","position":5,"is_corresponding":false},{"id":724409,"name":"Kathleen Gärtner","orcid":"0000-0003-2221-6251","position":6,"is_corresponding":false},{"id":382156,"name":"Rajendra Pahwa","orcid":null,"position":7,"is_corresponding":false},{"id":380953,"name":"Nicola Cotugno","orcid":"0000-0002-7748-1581","position":8,"is_corresponding":false},{"id":724408,"name":"Pablo Rojo","orcid":"0000-0002-0197-5462","position":9,"is_corresponding":false},{"id":576181,"name":"Eleni Nastouli","orcid":"0000-0002-1684-2013","position":10,"is_corresponding":false},{"id":80427,"name":"Nigel Klein","orcid":null,"position":11,"is_corresponding":false},{"id":438212,"name":"Caroline Foster","orcid":"0000-0001-8278-8564","position":12,"is_corresponding":false},{"id":724410,"name":"Anita De Rossi","orcid":"0000-0001-6435-7509","position":13,"is_corresponding":false},{"id":474555,"name":"Carlo Giaquinto","orcid":"0000-0001-9365-0413","position":14,"is_corresponding":false},{"id":380962,"name":"Paolo Rossi","orcid":"0000-0003-2620-7918","position":15,"is_corresponding":false},{"id":373975,"name":"Paolo Palma","orcid":"0000-0002-3066-4719","position":16,"is_corresponding":false},{"id":295814,"name":"Savita Pahwa","orcid":"0000-0002-4470-4216","position":17,"is_corresponding":false},{"id":522232,"name":"Stefano Rinaldi","orcid":"0000-0002-1499-4435","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:47:48.974996Z","pmid":"33901266","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}