{"doi":"10.4049/immunohorizons.2000051","title":"Activation-Induced Marker Expression Identifies <i>Mycobacterium tuberculosis</i>–Specific CD4 T Cells in a Cytokine-Independent Manner in HIV-Infected Individuals with Latent Tuberculosis","abstract":"Abstract HIV infection is a significant risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease, yet the mechanisms whereby HIV impairs T cell immunity to M. tuberculosis have not been fully defined. Evaluation of M. tuberculosis–specific CD4 T cells is commonly based on IFN-γ production, yet increasing evidence indicates the immune response to M. tuberculosis is heterogeneous and encompasses IFN-γ–independent responses. We hypothesized that upregulation of surface activation-induced markers (AIM) would facilitate detection of human M. tuberculosis–specific CD4 T cells in a cytokine-independent manner in HIV-infected and HIV-uninfected individuals with LTBI. PBMCs from HIV-infected and HIV-uninfected adults in Kenya were stimulated with CFP-10 and ESAT-6 peptides and evaluated by flow cytometry for upregulation of the activation markers CD25, OX40, CD69, and CD40L. Although M. tuberculosis–specific IFN-γ and IL-2 production was dampened in HIV-infected individuals, M. tuberculosis–specific CD25+OX40+ and CD69+CD40L+ CD4 T cells were detectable in the AIM assay in both HIV-uninfected and HIV-infected individuals with LTBI. Importantly, the frequency of M. tuberculosis–specific AIM+ CD4 T cells was not directly impacted by HIV viral load or CD4 count, thus demonstrating the feasibility of AIM assays for analysis of M. tuberculosis–specific CD4 T cells across a spectrum of HIV infection states. These data indicate that AIM assays enable identification of M. tuberculosis–specific CD4 T cells in a cytokine-independent manner in HIV-uninfected and HIV-infected individuals with LTBI in a high-tuberculosis burden setting, thus facilitating studies to define novel T cell correlates of protection to M. tuberculosis and elucidate mechanisms of HIV-associated dysregulation of antimycobacterial immunity.","journal":"ImmunoHorizons","year":2020,"id":70653,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":375234,"name":"Wendy Whatney","orcid":null,"position":1,"is_corresponding":false},{"id":362801,"name":"Jeremiah Khayumbi","orcid":null,"position":2,"is_corresponding":false},{"id":361298,"name":"Joshua Ongalo","orcid":"0000-0002-4968-6176","position":3,"is_corresponding":false},{"id":373855,"name":"Loren E. Sasser","orcid":"0000-0003-3348-9933","position":4,"is_corresponding":false},{"id":361299,"name":"Angela Campbell","orcid":"0000-0003-3990-3656","position":5,"is_corresponding":false},{"id":375235,"name":"Meghan Franczek","orcid":null,"position":6,"is_corresponding":false},{"id":373856,"name":"Mbuyi Madeleine Kabongo","orcid":"0000-0002-5158-6860","position":7,"is_corresponding":false},{"id":361301,"name":"Samuel Gurrion Ouma","orcid":"0000-0003-3559-9028","position":8,"is_corresponding":false},{"id":375236,"name":"Felix Odhiambo Hayara","orcid":null,"position":9,"is_corresponding":false},{"id":308895,"name":"Neel R. Gandhi","orcid":"0000-0002-1665-299X","position":10,"is_corresponding":false},{"id":362804,"name":"Cheryl L. Day","orcid":null,"position":11,"is_corresponding":false},{"id":375233,"name":"Morgan S. Barham","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:43:32.585486Z","pmid":"33008839","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":[]}