{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T18:56:50Z","timestamp":1774119410734,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>Mono- and multifunctional specific CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T-cell responses were evaluated to improve the immune-based detection of active tuberculosis (TB) and latent infection (LTBI). We applied flow cytometry to investigate cytokines profile (IFN-<jats:italic>\u03b3<\/jats:italic>, TNF-<jats:italic>\u03b1<\/jats:italic>, and IL-2) of T cells after stimulation with TB antigens in 28 TB-infected subjects (18 active TB and 10 LTBI) and 10 uninfected controls. Cytokines production by CD4<jats:sup>+<\/jats:sup>T cells at single-cell levels was higher in TB-infected subjects than uninfected controls<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mfenced separators=\"|\"><mml:mrow><mml:mi mathvariant=\"normal\">P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.0001<\/mml:mn><\/mml:mrow><\/mml:mfenced><\/mml:mrow><\/mml:math>. Assigning to activated CD4<jats:sup>+<\/jats:sup>T cells, producing any of the three cytokines, a cut-off &gt;0.45%, it was possible to differentiate TB-infected (&gt;0.45%) by uninfected subjects (&lt;0.45%). Among TB-infected subjects, the frequencies of multifunctional CD4<jats:sup>+<\/jats:sup>T cells, simultaneously producing all 3 cytokines, are lower in active TB than LTBI subjects<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mrow><mml:mfenced separators=\"|\"><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.003<\/mml:mn><\/mml:mrow><\/mml:mfenced><\/mml:mrow><\/mml:math>. Thus, assigning to triple-positive CD4<jats:sup>+<\/jats:sup>T cells a cut-off &lt;0.182%, TB-infected individuals could be classified as active TB subjects (&lt;0.182%) or LTBI subjects (&gt;0.182%). The magnitude of CD8<jats:sup>+<\/jats:sup>T-cell responses showed no differences between active TB and LTBI. Multifunctional CD4<jats:sup>+<\/jats:sup>T-cell responses could have the potential to identify at single time point subjects without TB infection and patients having active or latent TB.<\/jats:p>","DOI":"10.1155\/2015\/217287","type":"journal-article","created":{"date-parts":[[2015,8,4]],"date-time":"2015-08-04T02:26:51Z","timestamp":1438655211000},"page":"1-10","source":"Crossref","is-referenced-by-count":18,"title":["Multifunctional Analysis of CD4<sup>+<\/sup>T-Cell Response as Immune-Based Model for Tuberculosis Detection"],"prefix":"10.1155","volume":"2015","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7730-3953","authenticated-orcid":true,"given":"Miriam","family":"Lichtner","sequence":"first","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy"},{"name":"Infectious Diseases Unit, Sapienza University, Corso della Repubblica 79, 04100 Latina, 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