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However, their role in the course of <jats:italic>Neospora caninum<\/jats:italic> infection has not been fully elucidated. Here we report that CD8-deficient mice infected with <jats:italic>N. caninum<\/jats:italic> presented higher parasitic loads in the brain and lungs and lower spleen and brain immunity-related GTPases than their wild-type counterparts. Moreover, adoptive transfer of splenic CD8<jats:sup>+<\/jats:sup> T cells sorted from <jats:italic>N. caninum<\/jats:italic>-primed immunosufficient C57BL\/10 ScSn mice prolonged the survival of infected IL-12-unresponsive C57BL\/10 ScCr recipients. In both C57BL\/6 and C57BL\/10 ScSn mice CD8<jats:sup>+<\/jats:sup> T cells are activated and produce interferon-\u03b3 (IFN-\u03b3) upon challenged with <jats:italic>N. caninum.<\/jats:italic> The host protective role of IFN-\u03b3 produced by CD8<jats:sup>+<\/jats:sup> T cells was confirmed in <jats:italic>N. caninum<\/jats:italic>-infected RAG2-deficient mice reconstituted with CD8<jats:sup>+<\/jats:sup> T cells obtained from either IFN-\u03b3-deficient or wild-type donors. Mice receiving IFN-\u03b3-expressing CD8<jats:sup>+<\/jats:sup> T cells presented lower parasitic burdens than counterparts having IFN-\u03b3-deficient CD8<jats:sup>+<\/jats:sup> T cells. Moreover, we observed that <jats:italic>N. caninum<\/jats:italic>-infected perforin-deficient mice presented parasitic burdens similar to those of infected wild-type controls. Altogether these results demonstrate that production of IFN-\u03b3 is a predominant protective mechanism conferred by CD8<jats:sup>+<\/jats:sup> T cells in the course of neosporosis.<\/jats:p>","DOI":"10.1038\/srep14913","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T09:04:39Z","timestamp":1444381479000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Predominant role of interferon-\u03b3 in the host protective effect of CD8+ T cells against Neospora caninum infection"],"prefix":"10.1038","volume":"5","author":[{"given":"Alexandra","family":"Correia","sequence":"first","affiliation":[]},{"given":"Pedro","family":"Ferreirinha","sequence":"additional","affiliation":[]},{"given":"Sofia","family":"Botelho","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Belinha","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Leit\u00e3o","sequence":"additional","affiliation":[]},{"given":"\u00cdris","family":"Caramalho","sequence":"additional","affiliation":[]},{"given":"Luzia","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"\u00c1frica","family":"Gonz\u00e1lez-Fernand\u00e9z","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Appelberg","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Vilanova","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2015,10,9]]},"reference":[{"key":"BFsrep14913_CR1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1128\/CMR.00031-06","volume":"20","author":"JP Dubey","year":"2007","unstructured":"Dubey, J. P., Schares, G. & Ortega-Mora, L. M. Epidemiology and control of neosporosis and Neospora caninum. Clin Microbiol Rev 20, 323\u2013367 (2007).","journal-title":"Clin Microbiol Rev"},{"key":"BFsrep14913_CR2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijpara.2012.10.022","volume":"43","author":"MP Reichel","year":"2013","unstructured":"Reichel, M. P., Alejandra Ayanegui-Alcerreca, M., Gondim, L. F. & Ellis, J. T. What is the global economic impact of Neospora caninum in cattle - the billion dollar question. Int J Parasitol 43, 133\u2013142 (2013).","journal-title":"Int J Parasitol"},{"key":"BFsrep14913_CR3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.pt.2014.06.004","volume":"30","author":"SJ Goodswen","year":"2014","unstructured":"Goodswen, S. J., Kennedy, P. J. & Ellis, J. T. Discovering a vaccine against neosporosis using computers: is it feasible? 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