{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T20:33:56Z","timestamp":1786998836859,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,14]]},"group-title":"Immunology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["75N93019C00070"],"award-info":[{"award-number":["75N93019C00070"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tuberculosis (TB) remains the leading infectious cause of death worldwide, yet immunological protection against\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb) remain poorly understood. We performed integrated single-cell transcriptomics and functional T-cell cloning on paired bronchoalveolar lavage (BAL) and peripheral blood samples from those exposed to TB, using IGRA and PET-CT to study potentially protective responses across the spectrum of TB infection\/disease. Recent Mtb exposure alone was sufficient to remodel the pulmonary T-cell compartment. Longitudinal follow-up demonstrated that all participants who progressed to active TB had baseline PET-CT abnormalities, showing that PET-CT scan can be used to find those at high risk of progression. Furthermore, those who were PET-positive, but did not progress to active TB provide a natural model for protection, and exhibited enrichment of pulmonary cytotoxic CD8-associated T cells, identifying a candidate protective immune program. TAR-seq identified a discrete population of clonally expanded Mtb-responsive T cells and enabled direct linkage of antigen-responsive TCRs to transcriptional state through T cell cloning. Functional T-cell cloning further established a framework connecting antigen specificity, TCR sequence, and pulmonary cell state. Together, these findings provide a comprehensive atlas of human pulmonary T-cell immunity across the spectrum of TB, identify pulmonary immune features associated with durable control of infection, and establish an integrated platform for defining protective T-cell responses to inform next-generation TB vaccine development.\n                <\/jats:p>","DOI":"10.64898\/2026.08.10.743910","type":"posted-content","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T06:15:26Z","timestamp":1786774526000},"source":"Crossref","is-referenced-by-count":0,"title":["Lung Resident T Cells Across the Spectrum of TB Infection and Disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-2742","authenticated-orcid":false,"given":"Dylan","family":"Kain","sequence":"first","affiliation":[{"name":"University Health Network, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GW","family":"McElfresh","sequence":"additional","affiliation":[{"name":"Oregon National Primate Research Center, OHSU, Beaverton, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine H.","family":"Rott","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States"},{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Cansler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn M.","family":"Swarbrick","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Walzl","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelita","family":"Du Plessis","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Lewinsohn","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8092-3080","authenticated-orcid":false,"given":"Benjamin N.","family":"Bimber","sequence":"additional","affiliation":[{"name":"Oregon National Primate Research Center, OHSU, Beaverton, OR, USA"},{"name":"Vaccine and Gene Therapy Institute, OHSU, Beaverton, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Lewinsohn","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA"},{"name":"VA Portland Health Care System, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081713050567000_2026.08.10.743910v1.1","unstructured":"Global Tuberculosis Report 2025 Available online: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2025 (accessed on 10 March 2026)."},{"key":"2026081713050567000_2026.08.10.743910v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68507-3"},{"key":"2026081713050567000_2026.08.10.743910v1.3","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit790"},{"key":"2026081713050567000_2026.08.10.743910v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.69"},{"key":"2026081713050567000_2026.08.10.743910v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6363915"},{"key":"2026081713050567000_2026.08.10.743910v1.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.93"},{"key":"2026081713050567000_2026.08.10.743910v1.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011110"},{"key":"2026081713050567000_2026.08.10.743910v1.8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095939"},{"key":"2026081713050567000_2026.08.10.743910v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nri3259"},{"key":"2026081713050567000_2026.08.10.743910v1.10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00992"},{"key":"2026081713050567000_2026.08.10.743910v1.11","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041816"},{"key":"2026081713050567000_2026.08.10.743910v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2015.10.006"},{"key":"2026081713050567000_2026.08.10.743910v1.13","doi-asserted-by":"crossref","unstructured":"Kain, D. ; 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