{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:01:47Z","timestamp":1768827707560,"version":"3.49.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"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":[[2020,10,30]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A\/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A\/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A\/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-\u03b3 stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A\/B antibodies. Educated CD25+CD127\u2212 regulatory T cells (edu.Tregs) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg; anti-A\/B antibodies were not involved in the Treg-mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical\/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.<\/jats:p>","DOI":"10.1111\/cei.13482","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T03:15:48Z","timestamp":1592968548000},"page":"249-261","source":"Crossref","is-referenced-by-count":5,"title":["The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via PD-L1 induced by anti-A\/B ligation"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-5192","authenticated-orcid":false,"given":"K","family":"Iwasaki","sequence":"first","affiliation":[{"name":"Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Hamana","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Hiramitsu","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Okad","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Tomosugi","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Narumi","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Watarai","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Horimi","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Muraguchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,18]]},"reference":[{"key":"2021121023214990000_cei13482-bib-0001","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1681\/ASN.2014111120","article-title":"IgG donor-specific anti-human HLA antibody subclasses and kidney allograft antibody-mediated injury","volume":"27","author":"Lefaucheur","year":"2016","journal-title":"J Am Soc 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