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To explore the function of PKC-\u03b8 in a chronic persisting infection in which T cells are crucial for pathogen control, we infected BALB\/c PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>and PKC-\u03b8<jats:sup>+\/+<\/jats:sup>wild-type mice with<jats:italic>Toxoplasma gondii<\/jats:italic>. The PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice succumbed to necrotizing<jats:italic>Toxoplasma<\/jats:italic>encephalitis due to an insufficient parasite control up to day 40, whereas the wild-type mice survived. The number of<jats:italic>T. gondii<\/jats:italic>-specific CD4 and CD8 T cells was significantly reduced in the PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice, resulting in the impaired production of protective cytokines (gamma interferon, tumor necrosis factor) and antiparasitic effector molecules (inducible nitric oxide, gamma interferon-induced GTPase) in the spleen and brain. In addition, Th2-cell numbers were reduced in infected the PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice, paralleled by the diminished GATA3 expression of PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>CD4 T cells and reduced<jats:italic>T. gondii<\/jats:italic>-specific IgG production in serum and cerebrospinal fluid. Western blot analysis of splenic CD4 and CD8 T cells revealed an impaired activation of the NF-\u03baB, AP-1, and MAPK pathways in<jats:italic>T. gondii<\/jats:italic>-infected PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Adoptive transfer of wild-type CD4 plus CD8 T cells significantly protected PKC-\u03b8<jats:sup>\u2212\/\u2212<\/jats:sup>mice from death by increasing the numbers of gamma interferon-producing<jats:italic>T. gondii<\/jats:italic>-specific CD4 and CD8 T cells, illustrating a cell-autonomous, protective function of PKC-\u03b8 in T cells. These findings imply that PKC-\u03b8 inhibition drastically impairs<jats:italic>T. gondii<\/jats:italic>-specific T-cell responses with fatal consequences for intracerebral parasite control and survival.<\/jats:p>","DOI":"10.1128\/iai.01407-09","type":"journal-article","created":{"date-parts":[[2010,5,25]],"date-time":"2010-05-25T02:23:54Z","timestamp":1274754234000},"page":"3454-3464","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Protective<i>Toxoplasma gondii<\/i>-Specific T-Cell Responses Require T-Cell-Specific Expression of Protein Kinase C-Theta"],"prefix":"10.1128","volume":"78","author":[{"given":"Gopala","family":"Nishanth","sequence":"first","affiliation":[{"name":"Institut fu\u0308r Medizinische Mikrobiologie, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Sakowicz-Burkiewicz","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Medizinische Mikrobiologie, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Ha\u0308ndel","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Medizinische Mikrobiologie, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kliche","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Molekulare und Klinische Immunologie, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Molekulare und Klinische Immunologie, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Naumann","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Experimentelle Innere Medizin, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Deckert","sequence":"additional","affiliation":[{"name":"Abteilung fu\u0308r Neuropathologie, Universita\u0308tsklinikum Ko\u0308ln, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Schlu\u0308ter","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Medizinische Mikrobiologie, OvG Universita\u0308t Magdeburg, Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00179.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/08916930600907954"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.8.5126"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031022"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1629"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.4049\/jimmunol.163.8.4453","volume":"163","year":"1999","unstructured":"Caamano, J., J. 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Immunol."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.4049\/jimmunol.151.7.3672","volume":"151","year":"1993","unstructured":"Gazzinelli, R. T., I. Eltoum, T. A. Wynn, and A. Sher. 1993. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J. Immunol.151:3672-3681.","journal-title":"J. Immunol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"798","DOI":"10.4049\/jimmunol.157.2.798","volume":"157","year":"1996","unstructured":"Gazzinelli, R. T., M. Wysocka, S. Hieny, T. Scharton-Kersten, A. Cheever, R. Kuhn, W. M\u00fcller, G. Trinchieri, and A. Sher. 1996. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J. 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