{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:09:15Z","timestamp":1790226555810,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"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":[[2019,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Heparin-binding hemagglutinin (HBHA), a surface protein of Mycobacterium tuberculosis, is an attractive vaccine candidate and marker of protective immunity against tuberculosis, although the mechanisms underlying this protective immunity are not fully understood. Comparisons of the immune responses of latently M. tuberculosis\u2013infected (LTBI) subjects to those of patients with active tuberculosis (aTB) may help to identify surrogate markers of protection, as LTBI subjects are most often lifelong protected against the disease. HBHA was shown to induce strong Th1 responses and cytotoxic CD8+ responses in LTBI subjects, but additional mechanisms of control of M. tuberculosis infection remain to be identified. In this study, using HBHA-induced blast formation as a readout of specific T lymphocyte activation, we report the presence in M. tuberculosis\u2013infected subjects of HBHA-induced CD4+ T cell blasts that degranulate, as measured by surface capture of CD107a. This suggests the induction by HBHA of a CD4+ T cell subset with cytolytic function, and as nearly half of these cells also contained IFN-\u03b3, they had both Th1 and cytotoxic characteristics. We further identified a CD4+ T lymphocyte subset producing IFN-\u03b3 together with a combination of mediators of cytotoxicity, i.e., perforin, granzymes, and granulysin, and we called them polycytotoxic CD4+ T lymphocytes. Interestingly, whereas purified protein derivative induced such cells in both LTBI subjects and patients with aTB, HBHA-specific polycytotoxic CD4+ T lymphocytes were detected in LTBI subjects and not in patients with pulmonary aTB. To our knowledge, we thus identified a new HBHA-induced CD4+ T cell subset that may contribute to the control of M. tuberculosis infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1800840","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T22:35:31Z","timestamp":1545086131000},"page":"421-427","source":"Crossref","is-referenced-by-count":21,"title":["HBHA-Induced Polycytotoxic CD4+ T Lymphocytes Are Associated with the Control of <i>Mycobacterium tuberculosis<\/i> Infection in Humans"],"prefix":"10.1093","volume":"202","author":[{"given":"Laetitia","family":"Aerts","sequence":"first","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Selis","sequence":"additional","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Corbi\u00e8re","sequence":"additional","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-3672","authenticated-orcid":false,"given":"Kaat","family":"Smits","sequence":"additional","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Van Praet","sequence":"additional","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7697-6849","authenticated-orcid":false,"given":"Nicolas","family":"Dauby","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Maladies Infectieuses, Centre Hospitalier Universitaire Saint-Pierre, Universit\u00e9 Libre de Bruxelles , 1000 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-7256","authenticated-orcid":false,"given":"Emmanuelle","family":"Petit","sequence":"additional","affiliation":[{"name":"INSERM, U1019 , F-59019 Lille ,","place":["France"]},{"name":"CNRS, UMR8204 , F-59019 Lille ,","place":["France"]},{"name":"Universit\u00e9 de Lille , F-59019 Lille ,","place":["France"]},{"name":"Institut Pasteur de Lille, Centre d\u2019Infection et d\u2019Immunit\u00e9 de Lille , F-59019 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahavir","family":"Singh","sequence":"additional","affiliation":[{"name":"Lionex Diagnostics and Therapeutics , D-38023 Braunschweig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Locht","sequence":"additional","affiliation":[{"name":"INSERM, U1019 , F-59019 Lille ,","place":["France"]},{"name":"CNRS, UMR8204 , F-59019 Lille ,","place":["France"]},{"name":"Universit\u00e9 de Lille , F-59019 Lille ,","place":["France"]},{"name":"Institut Pasteur de Lille, Centre d\u2019Infection et d\u2019Immunit\u00e9 de Lille , F-59019 Lille ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violette","family":"Dirix","sequence":"additional","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Mascart","sequence":"additional","affiliation":[{"name":"Laboratoire de Vaccinologie et d\u2019Immunologie Mucosale, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]},{"name":"Clinique d\u2019Immunobiologie, H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles , 1070 Brussels ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"key":"2025030417560165800_r1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/502S2a","article-title":"Epidemiology: a mortal foe","volume":"502","author":"Paulson","year":"2013","journal-title":"Nature"},{"key":"2025030417560165800_r2","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/cid\/cit790","article-title":"Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials","volume":"58","author":"Mangtani","year":"2014","journal-title":"Clin. 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