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Although there is good evidence that immune cytotoxic T lymphocytes (CTL) kill target cells <jats:italic>in vitro, in vivo<\/jats:italic> it is debated whether antiviral activity of CD8<jats:sup>+<\/jats:sup> T cells is mediated via direct target cell lysis or via soluble mediators.<\/jats:p><jats:p>To demonstrate CD8<jats:sup>+<\/jats:sup> T cell\u2010mediated destruction of infected cells <jats:italic>in vivo<\/jats:italic> a specific cell\u2010internal releasable marker was used as label, <jats:italic>i.e<\/jats:italic>. the nucleoprotein (NP) of LCMV. Since LCMV is non\u2010cytopathic the viral NP will only be released in substantial amounts because of destruction of infected host cells by immune CTL. It is shown here that the amount of NP released from infected and <jats:sup>51<\/jats:sup>Cr\u2010labeled target cells <jats:italic>in vitro<\/jats:italic> correlated well with the amount of radioactivity released. Viral NP released <jats:italic>in vivo<\/jats:italic> by CTL is bound and masked by the anti\u2010NP antibodies that are produced very early and efficiently. However, NP could readily be detected in sera of LCMV\u2010infected CD8<jats:sup>+<\/jats:sup> competent mice that could not generate antibodies specific for the NP because they were treated with a depleting anti\u2010CD4 antibody. NP was also detected in the cerebrospinal fluid of mice suffering from CD8<jats:sup>+<\/jats:sup> T cell\u2010mediated lymphocytic choriomeningitis after intracerebral infection. NP titers in sera of anti\u2010CD4\u2010treated LCMV\u2010infected mice exhibited a peak around day 7\u20138 when CTL activity was highest. When mice were CD8 T cell\u2010depleted with anti\u2010CD8 monoclonal antibody or in LCMV\u2010carrier mice, no NP was detected in the serum. Highly activated LCMV\u2010specific CTL adoptively transfused to LCMV\u2010infected irradiated recipient mice also caused a time\u2010dependent release of NP into serum. This confirms that the CD8<jats:sup>+<\/jats:sup> population is responsible for the release of NP from infected host cells. These results represent an <jats:italic>in vivo<\/jats:italic> correlate of CTL\u2010mediated cytolysis and evidence that antiviral cytotoxic T cells are cytolytic <jats:italic>in vivo<\/jats:italic>. They also suggest that antibody responses to internal antigens of non\u2010cytopathic viruses may signal CD8<jats:sup>+<\/jats:sup> Tcell\u2010mediated destruction of infected host cells.<\/jats:p>","DOI":"10.1002\/eji.1830230722","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T19:03:53Z","timestamp":1172775833000},"page":"1540-1545","source":"Crossref","is-referenced-by-count":19,"title":["Lysis of infected cells <i>in vivo<\/i> by antiviral cytolytic T cells demonstrated by release of cell internal viral proteins"],"prefix":"10.1002","volume":"23","author":[{"given":"Diego","family":"Kyburz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Speiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Battegay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Hengartner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf M.","family":"Zinkernagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"254","volume-title":"The Pathogenesis of infectious disease","author":"Mims C. 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