{"doi":"10.1101/2021.09.14.460324","title":"The role of antigen recognition in the γδ T cell response at the controlled stage of <i>M. tuberculosis</i> infection","abstract":"Summary γδ T cells contribute to host immune defense uniquely; but how they function in different stages (e.g., acute versus chronic) of a specific infection remains unclear. As the role of γδ T cells in early, active Mycobacterium tuberculosis (Mtb) infection is well documented, we focused on elucidating the γδ T cell response in persistent or controlled Mtb infection. Systems analysis of circulating γδ T cells from a South African adolescent cohort identified a distinct population of CD8+ γδ T cells that expanded in this state. These cells had features indicative of persistent antigenic exposure but were robust cytolytic effectors and cytokine/chemokine producers. While these γδ T cells displayed an attenuated response to TCR-mediated stimulation, they expressed Natural Killer (NK) cell receptors and had robust CD16 (Fc γ RIIIA)-mediated cytotoxic response, suggesting alternative ways for γδ T cells to control this stage of the infection. Despite this NK- like functionality, the CD8+ γδ T cells consisted of highly expanded clones, which utilized TCRs with different V γ / δ pairs. Theses TCRs could respond to an Mtb-lysate, but not to phosphoantigens, which are components of Mtb-lysate that activate γδ T cells in acute Mtb infection, indicating that the CD8+ γδ T cells were induced in a stage-specific, antigen-driven manner. Indeed, trajectory analysis showed that these γδ T cells arose from naive cells that had traversed distinct differentiation paths in this infection stage. Importantly, increased levels of CD8+ γδ T cells were also found in other chronic inflammatory conditions, including cardiovascular disease and cancer, suggesting that persistent antigenic exposure may lead to similar γδ T cell responses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":219311,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"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":818549,"name":"John R. Valainis","orcid":null,"position":1,"is_corresponding":false},{"id":575623,"name":"Oliver Kask","orcid":"0000-0002-3946-6700","position":2,"is_corresponding":false},{"id":817879,"name":"Mané Ohanyan","orcid":"0000-0001-7376-4157","position":3,"is_corresponding":false},{"id":817880,"name":"Meng Sun","orcid":"0000-0002-5753-2775","position":4,"is_corresponding":false},{"id":524135,"name":"Huang Huang","orcid":"0000-0002-8377-4823","position":5,"is_corresponding":false},{"id":817881,"name":"Megha Dubey","orcid":"0000-0001-7119-6504","position":6,"is_corresponding":false},{"id":817882,"name":"Lotta von Boehmer","orcid":"0000-0001-8018-1814","position":7,"is_corresponding":false},{"id":817883,"name":"Elsa Solà","orcid":"0000-0001-6897-2760","position":8,"is_corresponding":false},{"id":74023,"name":"Xianxi Huang","orcid":"0000-0001-5978-5031","position":9,"is_corresponding":false},{"id":74139,"name":"Patricia K. Nguyen","orcid":"0000-0001-7170-9787","position":10,"is_corresponding":false},{"id":252307,"name":"Thomas J. Scriba","orcid":"0000-0002-0641-1359","position":11,"is_corresponding":false},{"id":3343,"name":"Mark M. Davis","orcid":"0000-0001-6868-657X","position":12,"is_corresponding":false},{"id":233129,"name":"Sean C. Bendall","orcid":"0000-0003-1341-2453","position":13,"is_corresponding":false},{"id":13001,"name":"Yueh‐hsiu Chien","orcid":"0000-0002-6014-1230","position":14,"is_corresponding":false},{"id":690904,"name":"Roshni Roy Chowdhury","orcid":"0000-0002-1561-1133","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T23:53:38.409982Z","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":[]}