{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:34:29Z","timestamp":1790728469195,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>One third of the global population is estimated to be latently infected with Mycobacterium tuberculosis. We performed a phase I randomized controlled trial of isoniazid preventive therapy (IPT) before revaccination with bacillus Calmette\u2013Gu\u00e9rin (BCG) in healthy, tuberculin skin test\u2013positive (\u226515-mm induration), HIV-negative South African adults. We hypothesized that preclearance of latent bacilli with IPT modulates BCG immunogenicity following revaccination. Frequencies and coexpression of IFN-\u03b3, TNF-\u03b1, IL-2, IL-17, and\/or IL-22 in CD4 T cells and IFN-\u03b3\u2013expressing CD8 T, \u03b3\u03b4 T, CD3+CD56+ NKT-like, and NK cells in response to BCG were measured using whole blood intracellular cytokine staining and flow cytometry. We analyzed 72 participants who were revaccinated with BCG after IPT (n = 33) or without prior IPT (n = 39). IPT had little effect on frequencies or cytokine coexpression patterns of M. tuberculosis\u2013 or BCG-specific responses. Revaccination transiently boosted BCG-specific Th1 cytokine-expressing CD4, CD8, and \u03b3\u03b4 T cells. Despite high frequencies of IFN-\u03b3\u2013expressing BCG-reactive CD3+CD56+ NKT-like cells and CD3\u2212CD56dim and CD3\u2212CD56hi NK cells at baseline, BCG revaccination boosted these responses, which remained elevated up to 1 y after revaccination. Such BCG-reactive memory NK cells were induced by BCG vaccination in infants, whereas in vitro IFN-\u03b3 expression by NK cells upon BCG stimulation was dependent on IL-12 and IL-18. Our data suggest that isoniazid preclearance of M. tuberculosis bacilli has little effect on the magnitude, persistence, or functional attributes of lymphocyte responses boosted by BCG revaccination. Our study highlights the surprising durability of BCG-boosted memory NKT-like and NK cells expressing antimycobacterial effector molecules, which may be novel targets for tuberculosis vaccines.<\/jats:p>","DOI":"10.4049\/jimmunol.1501996","type":"journal-article","created":{"date-parts":[[2016,7,14]],"date-time":"2016-07-14T06:52:18Z","timestamp":1468479138000},"page":"1100-1110","source":"Crossref","is-referenced-by-count":140,"title":["Bacillus Calmette\u2013Gu\u00e9rin (BCG) Revaccination of Adults with Latent <i>Mycobacterium tuberculosis<\/i> Infection Induces Long-Lived BCG-Reactive NK Cell Responses"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-576X","authenticated-orcid":false,"given":"Sara","family":"Suliman","sequence":"first","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2221-8997","authenticated-orcid":false,"given":"Hennie","family":"Geldenhuys","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L","family":"Johnson","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-2534","authenticated-orcid":false,"given":"Jane E","family":"Hughes","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Smit","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9906-0713","authenticated-orcid":false,"given":"Melissa","family":"Murphy","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Toefy","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-4101","authenticated-orcid":false,"given":"Lesedi","family":"Lerumo","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan","family":"Hopley","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Pienaar","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6738-4972","authenticated-orcid":false,"given":"Phalkun","family":"Chheng","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1662-4961","authenticated-orcid":false,"given":"Elisa","family":"Nemes","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F","family":"Hoft","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Departments of Internal Medicine and Molecular Biology, Saint Louis University Medical Center and Center for Vaccine Development , St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem A","family":"Hanekom","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5760-9595","authenticated-orcid":false,"given":"W Henry","family":"Boom","sequence":"additional","affiliation":[{"name":"Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hatherill","sequence":"additional","affiliation":[{"name":"South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town , Cape Town 7925,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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