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Knowledge of the key <jats:italic>Mtb<\/jats:italic> antigens and responding T\u2010cell subsets mediating protection against <jats:italic>Mtb<\/jats:italic> is critical for developing improved tuberculosis (TB) vaccines. We previously reported that <jats:italic>Mtb<\/jats:italic> DosR\u2010regulon\u2010encoded antigens are recognized well by human T cells in association with control of <jats:italic>Mtb<\/jats:italic> infection. The characteristics of the responding T\u2010cell subsets, however, remained unidentified. We have therefore studied the cytokine production and memory phenotypes of <jats:italic>Mtb<\/jats:italic> DosR\u2010regulon\u2010encoded antigen\u2010specific T cells from individuals who had been infected with <jats:italic>Mtb<\/jats:italic> decades ago, yet never developed TB (long\u2010term latent <jats:italic>Mtb<\/jats:italic>\u2010infected individuals). Using multi\u2010parameter flow cytometry and intracellular cytokine staining for IFN\u2010\u03b3, TNF\u2010\u03b1 and IL\u20102, we found double and single cytokine\u2010producing CD4<jats:sup>+<\/jats:sup> as well as CD8<jats:sup>+<\/jats:sup> T cells to be the most prominent subsets, particularly IFN\u2010\u03b3<jats:sup>+<\/jats:sup> TNF\u2010\u03b1<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cells. The majority of these T cells comprised effector memory and effector T cells. Furthermore, CFSE labeling revealed strong CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cell proliferative responses induced by several \u201cimmunodominant\u201d <jats:italic>Mtb<\/jats:italic> DosR antigens and their specific peptide epitopes. These findings demonstrate the prominent presence of double\u2010 and monofunctional CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cell responses in naturally protected individuals and support the possibility of designing <jats:italic>Mtb<\/jats:italic> DosR antigen\u2010based TB vaccines.<\/jats:p>","DOI":"10.1002\/eji.201141602","type":"journal-article","created":{"date-parts":[[2011,7,4]],"date-time":"2011-07-04T13:52:53Z","timestamp":1309787573000},"page":"2925-2936","source":"Crossref","is-referenced-by-count":81,"title":["Double\u2010 and monofunctional CD4<sup>+<\/sup> and CD8<sup>+<\/sup> T\u2010cell responses to <i>Mycobacterium tuberculosis<\/i> DosR antigens and peptides in long\u2010term latently infected individuals"],"prefix":"10.1002","volume":"41","author":[{"given":"Susanna","family":"Commandeur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May Y.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista E.","family":"van Meijgaarden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke H.","family":"Friggen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees L. 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