{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T22:33:39Z","timestamp":1773700419414,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Blockade of co\u2010stimulatory signals to <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells is extremely effective for the induction of transplantation tolerance in immunologically naive rodents. However, infections and inflammation compromise the efficacy of co\u2010stimulation blockade regimens for the induction of tolerance, thereby stimulating the rejection of allografts. Previous studies have shown that stimulation of innate immunity abrogates tolerance induction by preventing the deletion of alloreactive <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells that normally occurs during co\u2010stimulation blockade. Although inflammation prevents the deletion of alloreactive T cells during co\u2010stimulation blockade, it is not known if this resistance to cell death is the result of a mechanism intrinsic to the <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cell. Here, we used syngeneic bone marrow chimeric mice that contain a trace population of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell receptor transgenic alloreactive <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells to investigate the early apoptotic signature and activation status of alloreactive T cells following exposure to inflammatory signals during co\u2010stimulation blockade with an antibody specific for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>154. Our findings revealed that the presence of bacterial lipopolysaccharide during co\u2010stimulation blockade enhanced the early activation of alloreactive <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells, as indicated by the up\u2010regulation of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>69, suppressed <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>as ligand expression, and prevented apoptotic cell death. However, alloreactive <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells from lipopolysaccharide\u2010treated mice remained sensitive to Fas\u2010mediated apoptosis <jats:italic>in vitro<\/jats:italic>. These findings suggest that alloreactive T cells rescued from deletion during co\u2010stimulation blockade by inflammation are still sensitive to pro\u2010apoptotic signals and that stimulating these apoptotic pathways during co\u2010stimulation blockade may augment the induction of tolerance.<\/jats:p>","DOI":"10.1111\/imm.12044","type":"journal-article","created":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T23:13:29Z","timestamp":1354144409000},"page":"322-332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Alloreactive <scp>CD<\/scp>8 <scp>T<\/scp> cells rescued from apoptosis during co\u2010stimulation blockade by <scp>T<\/scp>oll\u2010like receptor stimulation remain susceptible to <scp>F<\/scp>as\u2010induced cell death"],"prefix":"10.1111","volume":"138","author":[{"given":"Bhavana","family":"Priyadharshini","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas B.","family":"Thornley","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.","family":"Daniels","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Medical School Worcester MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Cuthbert","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School Worcester MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond M.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Massachusetts Medical School Worcester MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale L.","family":"Greiner","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School Worcester MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Brehm","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine University of Massachusetts Medical School Worcester MA 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