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The decreasing frequencies of terminal effector (T<jats:sub>TE<\/jats:sub>) CD8<jats:sup>+<\/jats:sup>T cells may increase reactivation risk in persons latently infected with <jats:italic>Mycobacterium tuberculosis (Mtb)<\/jats:italic>. We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV\u2013TB patients. Here, we aimed to study <jats:italic>Mtb<\/jats:italic>\u2010specific cytotoxicity, IFN\u2010\u03b3 secretion, memory status of CD8<jats:sup>+<\/jats:sup>T cells, and their modulation by DHEA during HIV\u2013TB coinfection. CD8<jats:sup>+<\/jats:sup>T cells from HIV\u2013TB patients showed a more differentiated phenotype with diminished na\u00efve and higher effector memory and T<jats:sub>TE<\/jats:sub> T\u2010cell frequencies compared to healthy donors both in total and <jats:italic>Mtb<\/jats:italic>\u2010specific CD8<jats:sup>+<\/jats:sup>T cells. Notably, CD8<jats:sup>+<\/jats:sup>T cells from HIV\u2013TB patients displayed higher Terminal Effector (T<jats:sub>TE<\/jats:sub>) CD45RA<jats:sup>dim<\/jats:sup> proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD\u20101 expression levels on CD8<jats:sup>+<\/jats:sup>T cells from HIV\u2013TB patients increased although restricted to the CD27<jats:sup>+<\/jats:sup> population. Interestingly, DHEA plasma levels positively correlated with T<jats:sub>TE<\/jats:sub> in CD8<jats:sup>+<\/jats:sup>T cells and in vitro DHEA treatment enhanced <jats:italic>Mtb<\/jats:italic>\u2010specific cytotoxic responses and terminal differentiation in CD8<jats:sup>+<\/jats:sup>T cells from HIV\u2013TB patients. Our data suggest that HIV\u2013TB coinfection promotes a deficient CD8<jats:sup>+<\/jats:sup> T\u2010cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8<jats:sup>+<\/jats:sup>T\u2010cell functions during HIV\u2013TB coinfection.<\/jats:p>","DOI":"10.1002\/eji.201545545","type":"journal-article","created":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T12:49:14Z","timestamp":1433508554000},"page":"2529-2541","source":"Crossref","is-referenced-by-count":15,"title":["HIV\u2013TB coinfection impairs CD8<sup>+<\/sup> T\u2010cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses"],"prefix":"10.1002","volume":"45","author":[{"given":"Guadalupe V.","family":"Suarez","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA Universidad de Buenos Aires \u2010 CONICET  Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mat\u00edas T.","family":"Angerami","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA Universidad de Buenos Aires \u2010 CONICET  Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda B.","family":"Vecchione","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA Universidad de Buenos Aires \u2010 CONICET  Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Laufer","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y SIDA Universidad de Buenos Aires \u2010 CONICET  Argentina"},{"name":"Hospital Juan A. 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