Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease
Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantion in elderly patients and association with acute graft-versus-host disease
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DOI：
10.1182/blood-2007-03-079160
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发表时间：
2007-09-01
期刊：
影响因子：
20.3
通讯作者：
Barrett, A. John
中科院分区：
文献类型：
--
作者：
Mielke, Stephan;Rezvani, Katayoun;Barrett, A. John
使用抗CD 25免疫毒素（IT）选择性耗尽（SID）异基因干细胞移植（SCT）中的宿主反应性供体T细胞是预防急性移植物抗宿主病（aGvHD）的一种策略。人们担心，同时去除调节性T细胞（T-CTL）和不完全去除同种异体活化的CD 25（+）T细胞可能会增加aGvHD的风险。因此，我们测量了16例接受T细胞去除的同种异体移植物和抗CD 25-IT治疗的SD淋巴细胞的患者的血液中的T，g，在13个HLA相同的供体中，在10个SD产品中。通过细胞内叉头盒蛋白3（FOXP 3）染色和CD 4（+）细胞中FOXP 3基因的定量逆转录-聚合酶链反应（qRT-PCR）来表征T-T细胞。患者接受的SD T细胞中位数为1.0 × 10（8）/kg，干细胞产品中残留的T细胞中位数为0.25 × 10（4）/kg。SCT后TCFs迅速重建，并进一步扩张。SD产品中的CD 4（+）T细胞中，1.5%至4.8%为CD 25（-）T-T细胞。急性GvHD（>= II级）仅限于5例患者，其供体与无临床显著aGvHD的患者相比，具有显著（P = 0.019）更少的TcR。这些结果表明，SD同种异体移植后可发生快速T-reg重建，无论是来自CD 25（-）T-reg逃逸耗竭，还是来自干细胞产物中残留的CD 25（-）和CD 25（+）T-reg，这些干细胞产物在移植后扩增并可提供额外的抗GvHD保护。
Selective depletion (SID) of host-reactive donor T cells from allogeneic stem-cell transplants (SCTs) using an anti-CD25 immunotoxin (IT) is a strategy to prevent acute graft-versus-host disease (aGvHD). There is concern that concurrent removal of regulatory T cells (T-regs) with incomplete removal of alloactivated CD25(+) T cells could increase the risk of aGvHD. We therefore measured T,g, in the blood of 16 patients receiving a T-cell-depleted allograft together with anti-CD25-IT-treated SD lymphocytes, in 13 of their HLA-Identical donors, and in 10 SD products. T-regs were characterized by intracellular staining for forkhead box protein 3 (FOXP3) and by quantitative reversetranscription-polymerase chain reaction (qRT-PCR) for FOXP3 gene in CD4(+) cells. Patients received a median of 1.0 x 10(8)/kg SD T cells and a stem cell product containing a median of 0.25 x 10(4)/kg residual T cells. Tregs reconstituted promptly after SCT and underwent further expansion. Of the CD4(+) T cells in SD products, 1.5% to 4.8% were CD25(-) T-regs. Acute GvHD (>= grade II) was restricted to 5 patients whose donors had significantly (P = .019) fewer Tregs compared with those without clinically significant aGvHD. These results suggest that rapid T-reg reconstitution can occur following SD allografts, either from CD25(-) T-regs escaping depletion, or from residual CD25(-) and CD25(+) T-regs contained in the stem-cell product that expand after transplantation and may confer additional protection against GvHD.