{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:49:53Z","timestamp":1761630593860},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,1,11]],"date-time":"2012-01-11T00:00:00Z","timestamp":1326240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Renal allograft survival is related directly to cell senescence. In the transplantation scenario many cellular events \u2013 participating as immunological and non-immunological factors \u2013 could contribute to accelerate this biological process, responsible for the ultimate fate of the graft. Mechanisms concerned in tolerance versus rejection are paramount in this outcome. For this reason, immunosuppressive treatment constitutes an extremely important decision to prevent organ dysfunction and, finally, graft loss. This study was conducted to document the proportion of CD4+\/interleukin (IL)-17A+-, CD16+\/indoleamine 2, 3-dioxygenase (IDO+)-, forkhead box protein P3 (FoxP3+)-expressing cells, senescent cells (p16INK4\u03b1) and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol-Myers Squibb IM103008) study. CD4+\/IL-17A+, CD16+\/IDO+, FoxP3+ and p16INK4\u03b1+ cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre-implantation) and at 12 months post-transplant. Senescent cells and CD4+\/IL-17A+ cells were increased among graft biopsies in subjects receiving cyclosporin A (CsA) compared to those under belatacept treatment. Meanwhile, CD16+\/IDO+ and FoxP3+-expressing cells were lower in biopsies from CsA treatment compared to patients treated with Belatacept. Histological morphometric analyses disclosed more IF in 12-month CsA-treated patients in comparison to pre-implantation biopsy findings. Summing up, renal biopsies from patients receiving belatacept showed greater amounts of FoxP3+ cells and lower amounts of CD4+\/IL-17A+ and senescent cells compared to patients under CsA treatment. Along with these findings, an increase in IF in annual CsA-treated-patients biopsies compared to pre-implantation and belatacept-treated patients were observed.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2011.04504.x","type":"journal-article","created":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T13:17:19Z","timestamp":1318425439000},"page":"330-337","source":"Crossref","is-referenced-by-count":20,"title":["Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16<i>INK<\/i>4\u03b1 senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A"],"prefix":"10.1093","volume":"167","author":[{"given":"J","family":"Furuzawa-Carballeda","sequence":"first","affiliation":[{"name":"Department of Immunology and Rheumatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Alber\u00fa","sequence":"additional","affiliation":[{"name":"Department of Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Palafox","sequence":"additional","affiliation":[{"name":"Department of Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Uribe-Uribe","sequence":"additional","affiliation":[{"name":"Department of Pathology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L E","family":"Morales-Buenrostro","sequence":"additional","affiliation":[{"name":"Department of Transplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Reyes Acevedo","sequence":"additional","affiliation":[{"name":"Hospital Miguel Hidalgo, Aguascalientes"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Mondrag\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto Mexicano de Trasplantes, Morelos"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Chevaile","sequence":"additional","affiliation":[{"name":"Hospital Ignacio Morones Prieto, San Luis Potos\u00ed, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Llorente","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,1,11]]},"reference":[{"key":"2021122708455996300_b1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1600-6143.2005.00749.x","article-title":"Rational development of LEA29Y (belatacept), a high affinity variant of CTLA4-Ig with potent immunosuppressive 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