{"doi":"10.3389/fimmu.2021.712480","title":"Mycobacterium tuberculosis-Specific T Cell Functional, Memory, and Activation Profiles in QuantiFERON-Reverters Are Consistent With Controlled Infection","abstract":"Reversion of immune sensitization tests for Mycobacterium tuberculosis (M.tb) infection, such as interferon-gamma release assays or tuberculin skin test, has been reported in multiple studies. We hypothesized that QuantiFERON-TB Gold (QFT) reversion is associated with a decline of M.tb-specific functional T cell responses, and a distinct pattern of T cell and innate responses compared to persistent QFT+ and QFT- individuals. We compared groups of healthy adolescents (n=~30 each), defined by four, 6-monthly QFT tests: reverters (QFT+/+/-/-), non-converters (QFT-/-/-/-) and persistent positives (QFT+/+/+/+). We stimulated peripheral blood mononuclear cells with M.tb antigens (M.tb lysate; CFP-10/ESAT-6 and EspC/EspF/Rv2348 peptide pools) and measured M.tb-specific adaptive T cell memory, activation, and functional profiles; as well as functional innate (monocytes, natural killer cells), donor-unrestricted T cells (DURT: γδ T cells, mucosal-associated invariant T and natural killer T-like cells) and B cells by flow cytometry. Projection to latent space discriminant analysis was applied to determine features that best distinguished between QFT reverters, non-converters and persistent positives. No longitudinal changes in immune responses to M.tb were observed upon QFT reversion. M.tb-specific Th1 responses detected in reverters were of intermediate magnitude, higher than responses in QFT non-converters and lower than responses in persistent positives. About one third of reverters had a robust response to CFP-10/ESAT-6. Among those with measurable responses, lower proportions of T SCM (CD45RA+CCR7+CD27+) and early differentiated (CD45RA-) IFN-γ-TNF+IL-2- M.tb lysate-specific CD4+ cells were observed in reverters compared with non-converters. Conversely, higher proportions of early differentiated and lower proportions of effector (CD45RA-CCR7-) CFP10/ESAT6-specific Th1 cells were observed in reverters compared to persistent-positives. No differences in M.tb-specific innate, DURT or B cell functional responses were observed between the groups. Statistical modelling misclassified the majority of reverters as non-converters more frequently than they were correctly classified as reverters or misclassified as persistent positives. These findings suggest that QFT reversion occurs in a heterogeneous group of individuals with low M.tb-specific T cell responses. In some individuals QFT reversion may result from assay variability, while in others the magnitude and differentiation status of M.tb-specific Th1 cells are consistent with well-controlled M.tb infection.","journal":"Frontiers in Immunology","year":2021,"id":174730,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"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":714375,"name":"Pia Steigler","orcid":"0000-0001-8948-1493","position":1,"is_corresponding":false},{"id":661814,"name":"Tessa Lloyd","orcid":"0000-0001-7658-6157","position":2,"is_corresponding":false},{"id":577007,"name":"Virginie Rozot","orcid":"0000-0001-9757-1501","position":3,"is_corresponding":false},{"id":577918,"name":"Boitumelo Mosito","orcid":null,"position":4,"is_corresponding":false},{"id":662638,"name":"Constance Schreuder","orcid":null,"position":5,"is_corresponding":false},{"id":662637,"name":"Timothy D. Reid","orcid":null,"position":6,"is_corresponding":false},{"id":253349,"name":"Nicole Bilek","orcid":null,"position":7,"is_corresponding":false},{"id":302718,"name":"Morten Rühwald","orcid":"0000-0002-1597-441X","position":8,"is_corresponding":false},{"id":231886,"name":"Jason R. Andrews","orcid":"0000-0002-5967-251X","position":9,"is_corresponding":false},{"id":231909,"name":"Mark Hatherill","orcid":"0000-0003-3491-1809","position":10,"is_corresponding":false},{"id":403920,"name":"Francesca Little","orcid":"0000-0002-5917-9928","position":11,"is_corresponding":false},{"id":252307,"name":"Thomas J. Scriba","orcid":"0000-0002-0641-1359","position":12,"is_corresponding":false},{"id":424014,"name":"Elisa Nemes","orcid":"0000-0003-1662-4961","position":13,"is_corresponding":false},{"id":443981,"name":"Cheleka A. M. Mpande","orcid":"0000-0003-3438-2214","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:47:06.584146Z","pmid":"34526988","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":[]}