{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:11:45Z","timestamp":1768907505344,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,1,7]],"date-time":"2005-01-07T00:00:00Z","timestamp":1105056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HL-58688"],"award-info":[{"award-number":["RO1 HL-58688"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HL-67040"],"award-info":[{"award-number":["RO1 HL-67040"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Heme oxygenase\u20101 (HO\u20101), which degrades heme into three products (carbon monoxide, free iron, and biliverdin), plays a protective role in many models of disease via its anti\u2010inflammatory, anti\u2010apoptotic, and anti\u2010proliferative actions. Overexpression of HO\u20101 has been shown to suppress immune responses and prolong the survival of allografts; however, the underlying mechanism is not clear. We demonstrate two \u201cnew\u201d properties of HO\u20101 that mediate activation induced cell death (AICD) of allo\u2010antigen\u2010responsive murine CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, resulting in immunomodulation. First, it functions in vivo and in vitro to \u201cboost\u201d the proliferative response of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells to allo\u2010antigens in the early phase of allo\u2010antigen\u2010driven immune responses. This \u201cboosting\u201d effect is accompanied with a significant increase of activation markers and IL\u20102 production. Second, it exerts a pro\u2010apoptotic effect in those activated T cells after the initial burst of proliferation. We further show that the AICD effect is mediated through the Fas\/CD95\u2010FasL signal transduction pathway. Correlating with the above\u2010mentioned findings is the observed prolongation of mouse heart graft survival when HO\u20101 is expressed in vivo in both donor and recipient. In conclusion, induction of HO\u20101 expression accelerates clonal deletion of peripheral alloreactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells by promoting AICD, which is presumably a key mechanism for its immunomodulatory effects such as in prolonging the survival of transplanted organs.\n                  <\/jats:p>","DOI":"10.1096\/fj.04-2217fje","type":"journal-article","created":{"date-parts":[[2005,1,7]],"date-time":"2005-01-07T20:36:59Z","timestamp":1105130219000},"page":"1-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Heme oxygenase\u20101 modulates the allo\u2010immune response by promoting activation\u2010induced cell death of T cells"],"prefix":"10.1096","volume":"19","author":[{"given":"James","family":"Mcdaid","sequence":"first","affiliation":[{"name":"Immunobiology Research Center Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetss 02215"}]},{"given":"Kenichiro","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Immunobiology Research Center Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetss 02215"}]},{"given":"Angelo","family":"Chora","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia  2781\u2013901 Oeiras Portugal"}]},{"given":"Robert","family":"\u00d6llinger","sequence":"additional","affiliation":[{"name":"Immunobiology Research Center Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetss 02215"}]},{"given":"Terry B.","family":"Strom","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetss 02215"}]},{"given":"Xian C.","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Immunology Department of Medicine Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetss 02215"}]},{"given":"Fritz H.","family":"Bach","sequence":"additional","affiliation":[{"name":"Immunobiology Research Center Department of Surgery Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetss 02215"}]},{"given":"Miguel P.","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia  2781\u2013901 Oeiras Portugal"}]}],"member":"311","published-online":{"date-parts":[[2005,1,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/15260"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"5205","DOI":"10.4049\/jimmunol.162.9.5205","article-title":"Cell cycle-dependent regulation of FLIP levels and susceptibility to Fas-mediated apoptosis","volume":"162","author":"Algeciras-Schimnich A.","year":"1999","journal-title":"J. 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