{"doi":"10.1101/2021.12.17.473203","title":"CD4 T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection","abstract":"ABSTRACT The HIV-mediated decline in circulating CD4 T cells correlates with increased risk of active tuberculosis (TB) 1–4 . However, HIV/ Mycobacterium tuberculosis (Mtb) co-infected individuals also have an increased incidence of TB prior to loss of CD4 T cells in blood 3,5 , raising the possibility that HIV co-infection leads to disruption of CD4 T cell responses at the site of lung infection before they are observed systemically. Here we used a rhesus macaque model of SIV/Mtb co-infection to study the early effects of acute SIV infection on CD4 T cells in pulmonary Mtb granulomas. Two weeks after SIV co-infection CD4 T cells were dramatically depleted from granulomas, before significant bacterial outgrowth, disease reactivation as measured by PET-CT imaging, or CD4 T cell loss in blood, airways, and lymph nodes. Mtb-specific CD4 T cells, CCR5-expressing, in granulomas were preferentially depleted by SIV infection. Moreover, CD4 T cells were preferentially depleted from the granuloma core and lymphocyte cuff relative to B cell-rich regions, and live imaging of granuloma explants showed that SIV co-infection reduced T cell motility. Thus, Mtb-specific CD4 T cells in pulmonary granulomas may be decimated before many patients even experience the first symptoms of acute HIV infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219774,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"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":286113,"name":"Christine E Nelson","orcid":"0000-0003-3879-9105","position":1,"is_corresponding":false},{"id":286111,"name":"Keith D. Kauffman","orcid":"0000-0001-7208-1565","position":2,"is_corresponding":false},{"id":628487,"name":"Nickiana E. Lora","orcid":"0000-0002-3507-6262","position":3,"is_corresponding":false},{"id":341771,"name":"Caian L. Vinhaes","orcid":"0000-0003-3370-7128","position":4,"is_corresponding":false},{"id":819457,"name":"Danielle E. Dorosky","orcid":null,"position":5,"is_corresponding":false},{"id":286110,"name":"Shunsuke Sakai","orcid":"0000-0003-0344-9447","position":6,"is_corresponding":false},{"id":819015,"name":"Felipe Gómez","orcid":"0000-0001-9977-7060","position":7,"is_corresponding":false},{"id":819458,"name":"Joel D. Fleegle","orcid":null,"position":8,"is_corresponding":false},{"id":819459,"name":"Melanie Parham","orcid":null,"position":9,"is_corresponding":false},{"id":819016,"name":"Shehan Perera","orcid":"0000-0003-3921-6741","position":10,"is_corresponding":false},{"id":230241,"name":"Cecilia S. Lindestam Arlehamn","orcid":"0000-0001-7302-8002","position":11,"is_corresponding":false},{"id":55670,"name":"Alessandro Sette","orcid":"0000-0001-7013-2250","position":12,"is_corresponding":false},{"id":639789,"name":"Tuberculosis Imaging Program","orcid":null,"position":13,"is_corresponding":false},{"id":241757,"name":"Jason M. Brenchley","orcid":"0000-0001-8357-2984","position":14,"is_corresponding":false},{"id":382615,"name":"Artur T. L. Queiroz","orcid":"0000-0003-4908-9993","position":15,"is_corresponding":false},{"id":252301,"name":"Bruno B. Andrade","orcid":"0000-0001-6833-3811","position":16,"is_corresponding":false},{"id":243363,"name":"Juraj Kabát","orcid":"0000-0001-8636-542X","position":17,"is_corresponding":false},{"id":584801,"name":"Laura E. Via","orcid":"0000-0001-6074-9521","position":18,"is_corresponding":false},{"id":286114,"name":"Daniel L. Barber","orcid":"0000-0001-7008-7509","position":19,"is_corresponding":false},{"id":594809,"name":"Taylor W. Foreman","orcid":"0000-0003-2968-9019","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:42.928212Z","pmid":null,"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":[]}