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Here we show that, in contrast to previous findings, IFN-\u03b3 was produced by CD4<jats:sup>+<\/jats:sup>, but not CD8<jats:sup>+<\/jats:sup>, T cells in mice infected with<jats:named-content content-type=\"genus-species\">Trypanosoma brucei<\/jats:named-content>. Without any impairment in the secretion of IFN-\u03b3, infected CD8<jats:sup>\u2212\/\u2212<\/jats:sup>mice survived significantly longer than infected wild-type mice, suggesting that CD8<jats:sup>+<\/jats:sup>T cells mediated mortality in an IFN-\u03b3-independent manner. The increased survival of infected CD8<jats:sup>\u2212\/\u2212<\/jats:sup>mice was significantly reduced in the absence of IL-10 signaling. Interestingly, IL-10 was also secreted mainly by CD4<jats:sup>+<\/jats:sup>T cells. Strikingly, depletion of CD4<jats:sup>+<\/jats:sup>T cells abrogated the prolonged survival of infected CD8<jats:sup>\u2212\/\u2212<\/jats:sup>mice, demonstrating that CD4<jats:sup>+<\/jats:sup>T cells mediated protection. Infected wild-type mice and CD8<jats:sup>\u2212\/\u2212<\/jats:sup>mice depleted of CD4<jats:sup>+<\/jats:sup>T cells had equal survival times, suggesting that the protection mediated by CD4<jats:sup>+<\/jats:sup>T cells was counteracted by the detrimental effects of CD8<jats:sup>+<\/jats:sup>T cells in infected wild-type mice. Interestingly, CD4<jats:sup>+<\/jats:sup>T cells also mediated the mortality of infected mice in the absence of IL-10 signaling, probably via excessive secretion of IFN-\u03b3. Finally, CD4<jats:sup>+<\/jats:sup>, but not CD8<jats:sup>+<\/jats:sup>, T cells were critically involved in the synthesis of IgG antibodies during<jats:named-content content-type=\"genus-species\">T. brucei<\/jats:named-content>infections. Collectively, these results highlight distinct roles of CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells in the context of IFN-\u03b3 and IL-10 during<jats:named-content content-type=\"genus-species\">T. brucei<\/jats:named-content>infections.<\/jats:p>","DOI":"10.1128\/iai.00357-15","type":"journal-article","created":{"date-parts":[[2015,4,28]],"date-time":"2015-04-28T01:51:54Z","timestamp":1430185914000},"page":"2785-2795","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Distinct Contributions of CD4<sup>+<\/sup>and CD8<sup>+<\/sup>T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10"],"prefix":"10.1128","volume":"83","author":[{"given":"Gongguan","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donglei","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingshun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"},{"name":"Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Huan","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Breeding and Reproduction, South China Agricultural University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.06.010"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2011.01293.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2005.00791.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00675.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.08.040190.000503"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/264256a0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3024.1998.00156.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002089"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000078"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.44.1.107-111.1984"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2307\/3284033"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(00)01318-6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4049\/jimmunol.130.1.405","article-title":"Lymphocyte function in experimental African trypanosomiasis. 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