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In this study we demonstrate a novel mechanism by which human V\u03b42<jats:sup>+<\/jats:sup> \u03b3\u03b4 T cells are activated by the model pathogen Bacillus Calmette Gu\u00e9rin (BCG). We show <jats:italic>in vitro<\/jats:italic> that V\u03b42 cell cytokine production and cytotoxic activity in response to BCG are dependent on both dendritic cells (DCs) and memory CD4<jats:sup>+<\/jats:sup> \u03b1\u03b2 T cells (CD4 T cells). We found that V\u03b42 cells are indirectly activated by BCG in an interleukin (IL)\u201012p70\u2010dependent manner, and that DC production of the IL\u201012p70 responsible for V\u03b42 cell activation requires Toll\u2010like receptor 2\/4 ligands from BCG and interferon (IFN)\u2010\u03b3 from memory CD4 T cells. Our data suggest that V\u03b42 cell responses to BCG are dependent on the activation of IFN\u2010\u03b3\u2010producing memory CD4 T cells, and provide novel insight into the complex interplay between cells of the innate and adaptive immune response.<\/jats:p>","DOI":"10.1038\/icb.2013.30","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T10:14:34Z","timestamp":1372155274000},"page":"461-468","source":"Crossref","is-referenced-by-count":8,"title":["Tripartite immune cell co\u2010operation in the Bacillus Calmette Gu\u00e9rin\u2010induced activation of \u03b3\u03b4 T cells"],"prefix":"10.1111","volume":"91","author":[{"given":"Daniel W","family":"Fowler","sequence":"first","affiliation":[{"name":"St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Copier","sequence":"additional","affiliation":[{"name":"St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus G","family":"Dalgleish","sequence":"additional","affiliation":[{"name":"St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D","family":"Bodman\u2010Smith","sequence":"additional","affiliation":[{"name":"St George's University of London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,25]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830251025"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.11.1969"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.6044"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00479.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm031"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021500"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5481"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-007-0279-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-011-1121-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.7738"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.384354"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.11.012"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.7.4471"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-258558"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.11.5832"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261237"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425368"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231219"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.11.1593"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4238-4249.2003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.7.4798"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002040"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838366"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3057"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-010-0833-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.4.1211-1217.1995"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/146532402320219817"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"4984","DOI":"10.4049\/jimmunol.152.10.4984","article-title":"Primary activation of V gamma 9\u2010expressing gamma delta T cells by Mycobacterium tuberculosis. 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