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Here, we investigated the presence of multifunctional CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cells that expressed interferon gamma (IFN\u03b3), IL10 and tumor necrosis factor (TNF), or its combinations during dengue infection. Peripheral blood mononuclear cells (PBMCs) from outpatients with dengue (mild dengue forms) and hospitalized patients (or patients with dengue with warning signs and severe dengue) were cultured in the presence of envelope (ENV) or NS3 peptide libraries of DENV during critical (hospitalization period) and convalescence phases. The production of IFN\u03b3, IL10 and TNF by CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cells was assessed by flow cytometry. Our data show that patients with mild dengue, when compared with patients with dengue with warning signs and severe dengue, presented higher frequencies of multifunctional T\u2010cells like NS3\u2010specific IFN\u03b3\/IL10\u2010producing CD4<jats:sup>+<\/jats:sup> T\u2010cells in critical phase and NS3\u2010 and ENV\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cells producing IFN\u03b3\/IL10. In addition, NS3\u2010specific CD8<jats:sup>+<\/jats:sup> T\u2010cells producing high levels of IFN\u03b3\/TNF and IFN\u03b3\/TNF\/IL10 were also observed in the mild dengue group. We observed that multifunctional T\u2010cells produced higher levels of cytokines as measured by intracellular content when compared with single producer T\u2010cells. Importantly, multifunctional CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010cells producing IFN\u03b3, TNF and IL10 simultaneously displayed positive correlation with platelet levels, suggesting a protective role of this population. The presence of IL10<jats:sup>+<\/jats:sup>Th1 and IL10<jats:sup>+<\/jats:sup>Tc1 multifunctional cells was associated with mild dengue presentation, suggesting that these cells play a role in clinical evolution of dengue infection.<\/jats:p>","DOI":"10.1111\/imm.13185","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T07:07:36Z","timestamp":1583305656000},"page":"90-102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["T\u2010cells producing multiple combinations of IFN\u03b3, TNF and IL10 are associated with mild forms of dengue infection"],"prefix":"10.1111","volume":"160","author":[{"given":"Marcela Helena","family":"Gon\u00e7alves Pereira","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Marta","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Instituto Rene Rachou Funda\u00e7\u00e3o Oswaldo Cruz Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Pereira","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e9lcia Vasconcelos Barros","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Hospital Santa Casa BH Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Mafra","sequence":"additional","affiliation":[{"name":"Hospital Metropolitano Odilon Behrens Funda\u00e7\u00e3o Hospitalar do Estado de Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian Martins Oliveira","family":"Diniz","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina Universidade Federal de Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00daltimo Lib\u00e2nio","family":"da Costa","sequence":"additional","affiliation":[{"name":"Secretaria Municipal de Sa\u00fade Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Gollob","sequence":"additional","affiliation":[{"name":"International Research Center A. 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