{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:33:59Z","timestamp":1791318839606,"version":"4.3.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2002,2,5]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Background<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            CD4 T lymphocytes accumulate in unstable plaque. The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Methods and Results<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Gene profiling identified perforin, CD161, and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4\n            <jats:sup>+<\/jats:sup>\n            CD28\n            <jats:sup>null<\/jats:sup>\n            T cells, a T-cell subset that preferentially infiltrates unstable plaque. Frequencies of CD161\n            <jats:sup>+<\/jats:sup>\n            and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina (UA). CD161 appeared on CD4\n            <jats:sup>+<\/jats:sup>\n            CD28\n            <jats:sup>null<\/jats:sup>\n            T cells after stimulation, suggesting spontaneous activation of circulating CD4 T cells in UA. Perforin-expressing CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I\u2013recognizing killer-cell immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule exocytosis, as demonstrated by the paralyzing effect of pretreating CD4\n            <jats:sup>+<\/jats:sup>\n            CD28\n            <jats:sup>null<\/jats:sup>\n            T cells with strontium. Incubation of HUVECs with C-reactive protein (CRP) increased HUVEC lysis in a dose-dependent fashion.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Conclusions<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            In patients with UA, CD4 T cells undergo a change in functional profile and acquire cytotoxic capability. Cytotoxic CD4 T cells effectively kill endothelial cells; CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell\u2013mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization. The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes.\n          <\/jats:p>","DOI":"10.1161\/hc0502.103348","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:07Z","timestamp":1027898167000},"page":"570-575","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":267,"title":["T-Cell\u2013Mediated Lysis of Endothelial Cells in Acute Coronary Syndromes"],"prefix":"10.1161","volume":"105","author":[{"given":"Takako","family":"Nakajima","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Schulte","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Warrington","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Kopecky","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Frye","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u0308rg J.","family":"Goronzy","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M.","family":"Weyand","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (T.N., S.S., K.J.W., J.J.G., C.M.W.) and Immunology (K.J.W., J.J.G., C.M.W.) and Division of Cardiology (S.L.K., R.L.F.), Mayo Clinic, Rochester, Minn."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00045415-200008010-00007"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00308-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.92.7.1701"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(00)01339-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8651(05)70073-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(99)70246-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615543"},{"key":"e_1_3_2_8_2","first-page":"121","volume":"148","year":"1996","unstructured":"Li Z, Li L, Zielke HR, et al. 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