increase in CD19+CD24hiCD38hi transitional B lymphocytes compared with transplanted controls. Methods Ten patients from a phase 1 clinical trial who had received MIC infusions before kidney transplantation were followed to post-transplant day 1080. Results 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 in vitro 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 (P<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, in vitro 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. Conclusions 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. Clinical Trial registry name and registration number: MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1), NCT02560220...

中文翻译：

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肾移植受者体内经修饰的免疫细胞诱导持久的调节性 B 淋巴细胞


与移植对照相比，CD19+CD24hiCD38hi 移行 B 淋巴细胞增加。方法 对来自 1 期临床试验的 10 名在肾移植前接受 MIC 输注的患者进行随访，直至移植后第 1080 天。结果接受 MIC 治疗的患者具有良好的临床病程，未显示供者特异性人类白细胞抗原抗体或急性排斥反应。手术前 7 天接受最高剂量 MIC 并接受减少免疫抑制治疗的四名患者显示，体外淋巴细胞不存在针对刺激性供体血细胞的反应性，而针对第三方细胞的反应性得以保留。在这些患者中，移行 B 淋巴细胞的数量分别比 12 名接受最低限度免疫抑制的长期幸存者和 4 名手术耐受患者高 75 倍和 7 倍（两者 P<0.001）。此外，我们发现四分之三的患者中其他调节性 B 淋巴细胞亚群的数量显着增加，并且基因表达特征表明操作耐受性。在 MIC 治疗的患者中，B 淋巴细胞耗竭后，体外淋巴细胞对供体血细胞的反应性恢复，这表明调节性 B 淋巴细胞在供体特异性无反应中具有直接的病理生理作用。结论 这些结果表明，MIC 输注后供体特异性免疫抑制是持久的，并且与调节性 B 淋巴细胞的显着增加相关。供体来源的 MIC 似乎是一种免疫调节细胞群，在移植前给予受体时，可能会对肾移植产生有益的影响。 临床试验注册名称和注册号：用于活体肾移植受者个体化免疫抑制的 MIC 细胞疗法 (TOL-1)，NCT02560220...