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We have shown previously that <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb) peptides are presented by HLA\u2010E to CD8<jats:sup>+<\/jats:sup> effector T\u00a0cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA\u2010E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb\u2010peptide\/HLA\u2010E\u2010TM<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T\u00a0cells in the circulation of patients with active tuberculosis (TB). HLA\u2010E restricted CD8<jats:sup>+<\/jats:sup> T\u00a0cells from TB patients produced more IL\u201013 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8<jats:sup>+<\/jats:sup> T\u00a0cells, HLA\u2010E restricted cells produced more IFN\u03b3, IL\u20104, IL\u201010, and granulysin but less granzyme\u2010A. Moreover, compared to \u201cclassical\u201d Mtb specific HLA\u2010A2 restricted CD8<jats:sup>+<\/jats:sup> T\u00a0cells, HLA\u2010E restricted CD8<jats:sup>+<\/jats:sup> T\u00a0cells produced less TNF\u03b1 and perforin, but more IL\u20104. In conclusion, HLA\u2010E restricted\u2010 Mtb specific cells can produce Th2 cytokines directly.<\/jats:p>","DOI":"10.1002\/eji.201747184","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T02:52:39Z","timestamp":1510282359000},"page":"293-305","source":"Crossref","is-referenced-by-count":47,"title":["Detailed characterization of human <i>Mycobacterium tuberculosis<\/i> specific HLA\u2010E restricted CD8<sup>+<\/sup> T\u00a0cells"],"prefix":"10.1002","volume":"48","author":[{"given":"Teresa","family":"Prezzemolo","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"},{"name":"Central Laboratory for Advanced Diagnostics and Biomedical Research (CLADIBIOR) University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista E.","family":"van Meijgaarden","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees L.M.C.","family":"Franken","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Caccamo","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnostics and Biomedical Research (CLADIBIOR) University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Dieli","sequence":"additional","affiliation":[{"name":"Central Laboratory for Advanced Diagnostics and Biomedical Research (CLADIBIOR) University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H.M.","family":"Ottenhoff","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9878-0863","authenticated-orcid":false,"given":"Simone A.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002152"},{"key":"e_1_2_7_3_1","volume-title":"Global Tuberculosis report control 2016","author":"WHO","year":"2016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/314072"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3259"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.3.271"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.1987"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00070"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0819-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003432"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/142.3.442"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2695396"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095939"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201243262"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000782"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020609"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1161"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.4049\/jimmunol.149.9.2945","article-title":"The HLA\u2010E gene encodes two differentially regulated transcripts and a cell surface protein","volume":"149","author":"Ulbrecht M.","year":"1992","journal-title":"J. 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