{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:12:40Z","timestamp":1789074760570,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"Suppl 1","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,11,9]],"date-time":"2016-11-09T00:00:00Z","timestamp":1478649600000},"content-version":"vor","delay-in-days":282,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\/background:<\/jats:title>\n                    <jats:p>\n                      QuantiFERON-TB Gold In-Tube (QFT-GIT, Qiagen, Hilden, Germany) is an interferon-\u03b3 (IFN-\u03b3) release assay designed to detect latent tuberculosis infection (LTBI). Although QFT-GIT has several advantages (mainly that it is not affected by the Bacille Calmette\u2013Gu\u00e9rin vaccination), it has a poor sensitivity in immune-compromised individuals as it involves an immune response-based detection. Recently, QuantiFERON-TB Gold Plus (QFT-Plus) assay has been proposed as a new generation of QFT-GIT. QFT-Plus includes two tubes, TB1 and TB2 with\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      antigens to elicit a specific immune response. TB1 contains peptides derived from the antigens 6 kDa early secretory antigenic target (ESAT-6) and 10 kDa culture filtrate protein (CFP-10) (TB-7.7, present in QFT-GIT, has been removed), and it is designed to induce a specific CD4 T-cell response. TB2 contains newly designed peptides stimulating IFN-\u03b3 production by both CD4 and CD8 T cells. The additional peptides for eliciting CD8 T-cell responses have been included to increase the sensitivity of the test for LTBI detection. The aim of the study was to evaluate specific CD4 and CD8 T-cell responses to the\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      antigens contained within the QFT-Plus test by flow cytometry in individuals with active TB and LTBI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We enrolled 23 individuals with active TB and 30 individuals with LTBI. QFT-Plus assay and intracellular staining were performed. One million of peripheral blood mononuclear cells in 1 ml of complete medium (RPMI 1640) were dispensed in QFT-Plus tubes. Following 16\u201324 h stimulation, antigen-specific T cells were characterized by flow cytometry evaluating CD4, CD8, CD3 markers, and IFN-\u03b3 production. For statistical analysis, nonparametric tests were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We found that CD4 T-cell responses were induced by both TB1 and TB2. Differently, the CD8 T-cell response was mainly induced by TB2 and was significantly higher than that induced by TB1 (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.01). The frequency of Mtb specific T-cells observed in individuals with active TB was significantly higher than in those with LTBI (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.04). Finally, TB2-specific CD8 T-cell responses in individuals with active TB were associated with high radiological severity of lung lesions and microbiological diagnosis (based on\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      isolation in sputum culture).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This is the first characterization of CD4 and CD8 T-cell responses to QFT-Plus TB1 and TB2 tubes in individuals with active TB and LTBI enrolled in a low TB-endemic country such as Italy. We demonstrated that the increased sensitivity is a consequence of the ability of TB2 to induce a CD8 T-cell response which is mainly associated with active TB. This assay has the potential to be very useful in conditions of immune depression due to CD4 T-cell impairments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ijmyco.2016.09.063","type":"journal-article","created":{"date-parts":[[2016,11,11]],"date-time":"2016-11-11T18:18:38Z","timestamp":1478888318000},"page":"S25-S26","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of the CD4 and CD8 T-cell response in the QuantiFERON-TB Gold Plus kit"],"prefix":"10.4103","volume":"5","author":[{"given":"Elisa","family":"Petruccioli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Chiacchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Pepponi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vanini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Urso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Cuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Barcellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Palmieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela M.","family":"Cirillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ippolito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia","family":"Goletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["The International Journal of Mycobacteriology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S2212553116302011?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S2212553116302011?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ovid.com\/01929415-201605001-00018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:00:20Z","timestamp":1789074020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01929415-201605001-00018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":0,"journal-issue":{"issue":"Suppl 1","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1016\/j.ijmyco.2016.09.063","relation":{},"ISSN":["2212-5531","2212-554X"],"issn-type":[{"value":"2212-5531","type":"print"},{"value":"2212-554X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2]]}}}