{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T17:17:23Z","timestamp":1779124643369,"version":"3.51.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intestinal intraepithelial lymphocytes (IELs) are known to exert strong constitutive cytotoxic activity. In the present study we compared the Ag-specific cytotoxic activity and the effector mechanisms involved in non-Ag-primed, naive and in in vivo-primed IELs and splenic CD8 T cells. Ex vivo isolated naive CD8\u03b1\u03b1 TCR\u03b1\u03b2 IELs, CD8\u03b1\u03b2 IELs, and splenocytes from lymphocytic choriomeningitis virus (LCMV)-specific TCR transgenic mice exert Ag-specific cytotoxic activity in a long-term, but not in a short-term, cytotoxicity assay. This cytotoxic activity is mainly Fas-Fas ligand mediated and is significantly reduced in the presence of 20 \u03bcg\/ml Fas-Fc\u03b31 fusion protein. Both CD8\u03b1\u03b2 IELs and CD8\u03b1\u03b2 splenocytes isolated from LCMV-infected C57BL\/6 mice exert potent perforin-dependent cell-mediated cytotoxicity. CD8\u03b1\u03b1 TCR\u03b1\u03b2 IELs from LCMV-infected animals, however, show only minimal Ag-specific cytotoxicity. The potent cytotoxic activity of in vivo activated CD8\u03b1\u03b2 IELs is not affected by the addition of Fas-Fc\u03b31. Nevertheless CD8\u03b1\u03b2 IELs from LCMV-infected perforin-deficient mice exert Ag-specific cytotoxicity in a short-term cytotoxicity assay, and this cytotoxicity is almost completely blocked by the addition of Fas-Fc\u03b31. These results demonstrate that naive CD8\u03b1\u03b2 IELs exert Ag-specific, Fas-Fas ligand-mediated, constitutive cytotoxic activity in a long-term cytotoxicity assay, whereas primed CD8\u03b1\u03b2 IELs primarily use the perforin-dependent exocytosis pathway to exert their potent cytotoxic activity. Furthermore, these results clearly illustrate the requirement for Ag-specific determination of IEL-mediated cytotoxicity, because the elevated, but variable, frequencies of memory-type T cells in this compartment may lead to ambiguous results when polyclonal activation or redirected assays are used.<\/jats:p>","DOI":"10.4049\/jimmunol.164.1.398","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T18:07:57Z","timestamp":1398103677000},"page":"398-403","source":"Crossref","is-referenced-by-count":27,"title":["Differential Contribution of Fas- and Perforin-Mediated Mechanisms to the Cell-Mediated Cytotoxic Activity of Naive and In Vivo-Primed Intestinal Intraepithelial Lymphocytes"],"prefix":"10.1093","volume":"164","author":[{"given":"Nadia","family":"Corazza","sequence":"first","affiliation":[{"name":"Institute of Pathology, Division of Immunopathology, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Mu\u0308ller","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Division of Immunopathology, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Brunner","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Division of Immunopathology, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Ka\u0308gi","sequence":"additional","affiliation":[{"name":"Ontario Cancer Institute\/Amgen Institute , Toronto, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Mueller","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Division of Immunopathology, University of Bern , Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,1,1]]},"reference":[{"key":"2026020906022702000_R1","first-page":"1765","volume-title":"J. 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