{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:35:18Z","timestamp":1790717718130,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2023,1]]},"abstract":"\n Significance Statement<\/jats:title>\n \n In previous work, the authors demonstrated that kidney transplant recipients developed donor-specific unresponsiveness when they were given a pretransplant infusion of modified donor-derived PBMCs. In this study, they provide evidence that the immunosuppressive properties of these cells persist and the donor-specific unresponsiveness is long-lasting. In the four patients who received the highest dose of the modified immune cells, administration of these cells was associated with a striking increase in IL-10\u2013producing regulatory B lymphocytes and evidence of the consensus gene expression signature of operational tolerance.\n In vitro<\/jats:italic>\n , donor-specific unresponsiveness was abolished after B lymphocyte depletion, suggesting a direct pathophysiologic role for regulatory B lymphocytes. These findings support the notion that modified donor-derived PBMCs may be useful in kidney transplantation, but this approach requires further validation and rigorous controlled randomized studies.\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n We recently demonstrated that donor-derived modified immune cells (MICs)\u2014PBMCs that acquire immunosuppressive properties after a brief treatment\u2014induced specific immunosuppression against the allogeneic donor when administered before kidney transplantation. We found up to a 68-fold increase in CD19\n +<\/jats:sup>\n CD24\n hi<\/jats:sup>\n CD38\n hi<\/jats:sup>\n transitional B lymphocytes compared with transplanted controls.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Ten patients from a phase 1 clinical trial who had received MIC infusions before kidney transplantation were followed to post-transplant day 1080.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients treated with MICs had a favorable clinical course, showing no donor-specific human leukocyte antigen antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of\n in vitro<\/jats:italic>\n lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and seven-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively (\n P<\/jats:italic>\n <0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients,\n in vitro<\/jats:italic>\n lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiologic role of regulatory B lymphocytes in donor-specific unresponsiveness.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population that when administered to recipients before transplantation, may exert a beneficial effect on kidney transplants.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1), NCT02560220<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2022020210","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T15:35:12Z","timestamp":1663860912000},"page":"160-174","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":11,"title":["Induction of Long-Lasting Regulatory B Lymphocytes by Modified Immune Cells in Kidney Transplant Recipients"],"prefix":"10.1681","volume":"34","author":[{"given":"Christian","family":"Morath","sequence":"first","affiliation":[{"name":"Department of Nephrology, Heidelberg 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