{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:20:04Z","timestamp":1779243604637,"version":"3.51.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2003,3,1]],"date-time":"2003-03-01T00:00:00Z","timestamp":1046476800000},"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":[[2003,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The CD134-CD134 ligand (CD134L) costimulatory pathway has been shown to be critical for both T and B cell activation; however, its role in regulating the alloimmune response remains unexplored. Furthermore, its interactions with other costimulatory pathways and immunosuppressive agents are unclear. We investigated the effect of CD134-CD134L pathway blockade on allograft rejection in fully MHC-mismatched rat cardiac and skin transplantation models. CD134L blockade alone did not prolong graft survival compared with that of untreated recipients, and in combination with donor-specific transfusion, cyclosporine, or rapamycin, was less effective than B7 blockade in prolonging allograft survival. However, in combination with B7 blockade, long-term allograft survival was achieved in all recipients (&amp;gt;200 days). Moreover, this was synergistic in reducing the frequency of IFN-\u03b3-producing alloreactive lymphocytes and inhibiting the generation of activated\/effector lymphocytes. Most impressively, this combination prevented rejection in a presensitized model using adoptive transfer of primed lymphocytes into athymic heart transplant recipients. In comparison to untreated recipients (mean survival time (MST): 5.3 \u00b1 0.5 days), anti-CD134L mAb alone modestly prolonged allograft survival (MST: 14 \u00b1 2.8 days) as did CTLA4Ig (MST: 21.5 \u00b1 1.7 days), but all grafts were rejected within 24 days. Importantly, combined blockade further and significantly prolonged allograft survival (MST: 75.3 \u00b1 12.7 days) and prevented the expansion and\/or persistence of primed\/effector alloreactive T cells. Our data suggest that CD134-CD134L is a critical pathway in alloimmune responses, especially recall\/primed responses, and is synergistic with CD28-B7 in mediating T cell effector responses during allograft rejection. Understanding the mechanisms of collaboration between these different pathways is important for the development of novel strategies to promote long-term allograft survival.<\/jats:p>","DOI":"10.4049\/jimmunol.170.6.2949","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:21:23Z","timestamp":1398036083000},"page":"2949-2955","source":"Crossref","is-referenced-by-count":65,"title":["The Role of the CD134-CD134 Ligand Costimulatory Pathway in Alloimmune Responses In Vivo"],"prefix":"10.1093","volume":"170","author":[{"given":"Xueli","family":"Yuan","sequence":"first","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan D","family":"Salama","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Dong","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabela","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nader","family":"Najafian","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Chandraker","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisaya","family":"Akiba","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed H","family":"Sayegh","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics and Transplantation, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,3,15]]},"reference":[{"key":"2026020210115779900_R1","first-page":"1801","volume-title":"J. 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