{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:16:53Z","timestamp":1790727413313,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,12,10]]},"abstract":"<jats:p>\n                    \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    -Microglobulin-deficient (\u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) mice generate a CD4\n                    <jats:sup>+<\/jats:sup>\n                    major histocompatibility complex class II-restricted cytotoxic T-lymphocyte (CTL) response following infection with lymphocytic choriomeningitis (LCM) virus (LCMV). We have determined the cytotoxic mechanism used by these CD4\n                    <jats:sup>+<\/jats:sup>\n                    CTLs and have examined the role of this cytotoxic activity in pathogenesis of LCM disease in \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice. Lysis of LCMV-infected target cells by CTLs from \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice is inhibited by addition of soluble Fas-Ig fusion proteins or by pretreatment of the CTLs with the protein synthesis inhibitor emetine. In addition, LCMV-infected cell lines that are resistant to anti-Fas-induced apoptosis are refractory to lysis by these virus-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    CTLs. These data indicate that LCMV-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    CTLs from \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice use a Fas-dependent lytic mechanism. Intracranial (i.c.) infection of \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice with LCMV results in loss of body weight. Fas-deficient \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    .\n                    <jats:italic>lpr<\/jats:italic>\n                    mice develop a similar wasting disease following i.c. infection. This suggests that Fas-dependent cytotoxicity is not required for LCMV-induced weight loss. A potential mediator of this chronic wasting disease is tumor necrosis factor (TNF)-\u03b1, which is produced by LCMV-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    CTLs. In contrast to LCMV-induced weight loss, lethal LCM disease in \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice is dependent on Fas-mediated cytotoxicity. Transfer of immune splenocytes from LCMV-infected \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice into irradiated infected \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    mice results in death of recipient animals. In contrast, transfer of these splenocytes into irradiated infected \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    m\n                    <jats:sup>\u2212<\/jats:sup>\n                    .\n                    <jats:italic>lpr<\/jats:italic>\n                    mice does not cause death. Thus a role for CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell-mediated cytotoxicity in virus-induced immunopathology has now been demonstrated.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.25.14730","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"14730-14735","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Fas-dependent CD4\n                    <sup>+<\/sup>\n                    cytotoxic T-cell-mediated pathogenesis during virus\u2009infection"],"prefix":"10.1073","volume":"93","author":[{"given":"Allan\u2009J.","family":"Zajac","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology, and Medicine, University of North Carolina, Chapel Hill, NC 27599; and Department of Microbiology and Immunology, Loyola University, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u2009G.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology, and Medicine, University of North Carolina, Chapel Hill, NC 27599; and Department of Microbiology and Immunology, Loyola University, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip\u2009L.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology, and Medicine, University of North Carolina, Chapel Hill, NC 27599; and Department of Microbiology and Immunology, Loyola University, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey\u2009A.","family":"Frelinger","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology, and Medicine, University of North Carolina, Chapel Hill, NC 27599; and Department of Microbiology and Immunology, Loyola University, Maywood, IL 60153"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,12,10]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7518614"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90063-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.207"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.07.110191.002403"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.4049\/jimmunol.153.6.2506","volume":"153","author":"Walsh C M","year":"1994","unstructured":"C M Walsh, A A Glass, V Chiu, W R Clark J Immunol 153, 2506\u20132514 (1994).","journal-title":"J Immunol"},{"key":"e_1_3_2_6_2","first-page":"965","volume-title":"Fundamental Immunology","author":"Berke G","year":"1993","unstructured":"G Berke Fundamental Immunology, ed W E Paul (Raven, New York), pp. 965\u20131014 (1993)."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(90)90019-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/369031a0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","unstructured":"Walsh C.\u2009M. 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