FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion
FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion
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DOI：
10.1097/01.tp.0000266908.37446.02
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发表时间：
2007-06-27
期刊：
影响因子：
6.2
通讯作者：
Miller, Joshua
中科院分区：
文献类型：
--
作者：
Cirocco, Robert E.;Carreno, Manuel R.;Miller, Joshua
背景资料。我们更新了63例围手术期输入供体椎体骨髓(DBMC-I)的受者与219例具有相同免疫抑制和人口学特征的非输注对照受者更有利的10年已故供者肾移植存活率。我们质疑这是否与DBMC-I与未输血对照组的假定调节性FoxP3 mRNA和细胞表型(CD4(+)CD25(+高)百分比和高DC2：Dc1比率)有关。采用流式细胞仪检测外周血淋巴细胞(PBL)和骨髓中CD4(+)CD25(+HIGH)百分率和DC2：Dc1，用实时定量聚合酶链式反应(RT-PCR)检测CD3(+)细胞中FoxP3基因的表达。对大多数保留移植物功能的10年患者的PBL进行了类似的研究：21例(剩余37例)DBMC-I与55例(其余105例)对照。在正常受试者中，骨髓中的所有参数都显著高于外周血中的参数，这支持了我们之前关于体外DBMC免疫调节的报道。在移植后9.8+/-0.02年，DBMC-I组与对照组相比，移植失败率分别为17.5%和32.9%(P=0.02)，分别为247.6+/-24和79.9+/-3.1(平均值+/-SE)FoxP3拷贝/5,000 CD3(+)细胞(P=0.0001)。与FoxP3水平较低的终末期肾病患者(40.8+/-5.9，P<；0.0001)相比，两组受者的PBLCD4(+)CD25(+High)百分比均较低，但Dc2：Dc1值较高，这与移植后长期产生的非CD4(+)CD25(+High)T细胞一致。在DBMC-I组中，个体较高的FoxP3值与较高的髂骨嵌合率相关，但在对照组(嵌合率降低50倍)中则不相关。在慢性排斥对照中，FOY-P3进一步降低。在迄今尚不清楚的调节细胞表型中，移植周DBMC-I有较高的10年肾移植接受率、嵌合体和FoxP3 mRNA。
Background. We update more favorable 10-year deceased donor kidney transplant survival in 63 recipients infused perioperatively with donor vertebral body bone marrow (DBMC-i) vs. 219 noninfused controls having equivalent immunosuppression and demographics. We questioned if this was associated with putatively regulatory FoxP3 mRNA and cell phenotypes (CD4(+)CD25(+high) percentages and high DC2:DC1 ratios) in DBMC-i vs. noninfused controls.Methods. Baseline studies were performed on peripheral blood lymphocytes (PBLs) vs. marrow in normal laboratory volunteers of CD4(+)CD25(+high) percentages and DC2:DC1 by flow cytometry, and FoxP3 mRNA in CD3(+) cells by real-time polymerase chain reaction. Similar studies were performed on PBL of the majority of the 10-year patients remaining with graft function: 21 (of the remaining 37) DBMC-i vs. 55 (of the remaining 105) controls.Results. In normal subjects, all parameters were significantly higher in marrow than in PBL, supporting our previous reports of ex vivo DBMC immunoregulation. At 9.8 +/- .02 years posttransplant in DBMC-i vs. controls, death-censored percent graft failure was 17.5% vs. 32.9% (P= 0.02) with 247.6 +/- 24 vs. 79.9 +/- 3.1 (mean +/- SE) FoxP3 copies/5,000 CD3(+) cells (P= 0.0001). PBL CD4(+) CD25(+high) percentages were lower, but DC2:DC1 values higher in both recipient groups than in end-stage renal disease patients who had lower FoxP3 levels (40.8 +/- 5.9, P < 0.0001), consistent with non-CD4(+) CD25(+high) T regulatory cells generated long-term posttransplant. Individual higher FoxP3 values correlated with higher iliac crest chimerism in DBMC-i, but not in controls (with 50-fold lower chimerism). In chronically rejecting controls, Foy-P3 was further decreased.Conclusions. Peritransplant DBMC-i has higher 10-year renal transplant acceptance, chimerism, and FoxP3 mRNA in thus-far unclarified regulatory cell phenotypes.