{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:22:22Z","timestamp":1782235342668,"version":"3.54.5"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T00:00:00Z","timestamp":1510185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007560","name":"Chiesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Blockade of the CD80\/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28\u2212 T cells, which express CD57, are not susceptible to belatacept treatment. High numbers of CD4+CD57+programmed death 1 (PD-1)\u2212 T cells pretransplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of fluorescence activated cell sorted (FACS) CD4+CD57+PD-1\u2212 and CD8+CD57+PD-1\u2212 T cells, and their CD57\u2212 control populations, after alloantigen stimulation. The effect of belatacept on the cytotoxic capacity of pretransplantation peripheral blood mononuclear cells from 20 patients who received belatacept post-transplantation was also tested. Expression of co-inhibitory molecule CD223 increased by approximately 10-fold after allogeneic stimulation in all four T cell subsets. Proliferation and up-regulation of CD244 and PD-1 was observed for CD4+CD57\u2212PD-1\u2212 T cells after allogeneic stimulation, but no up-regulation of these markers occurred on CD8+ T cells or CD4+CD57+PD-1\u2212 T cells. However, CD4+CD57+PD-1\u2212 T cells and, to a lesser extent, CD8+CD57+PD-1\u2212 T cells displayed higher cytotoxicity as indicated by granzyme B expression. Belatacept inhibited the cytotoxic potential of CD4+CD57+PD-1\u2212 T cells (median of inhibition 31%, P &amp;lt; 0\u00b701) and CD8+CD57+PD-1\u2212 T cells (median of inhibition 10%, P &amp;lt; 0\u00b705). In conclusion, alloantigen-activated CD4+CD57+PD-1\u2212 T cells exhibited a less proliferative but more cytotoxic profile than their CD57\u2212 counterparts. Their cytotoxic capacity can be inhibited partly by belatacept and was not associated with development of rejection after kidney transplantation.<\/jats:p>","DOI":"10.1111\/cei.13070","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T11:32:55Z","timestamp":1507894375000},"page":"363-372","source":"Crossref","is-referenced-by-count":8,"title":["Co-inhibitory profile and cytotoxicity of CD57+PD-1\u2212 T cells in end-stage renal disease patients"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0641-9462","authenticated-orcid":false,"given":"R","family":"Kraaijeveld","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G N","family":"de Graav","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus MC, University Medical 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