Castermans Emilie, Baron Frédéric, Willems Evelyne, Schaaf-Lafontaine Nicole, Meuris Nathalie, Gothot André, Vanbellighen Jean-François, Herens Christian, Seidel Laurence, Geenen Vincent, Cheynier Remi, Beguin Yves
Department of Medicine, Division of Hematology, University of Liège, Liège, Belgium.
Haematologica. 2008 Feb;93(2):240-7. doi: 10.3324/haematol.11708. Epub 2008 Jan 26.
Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning.
Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC).
CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001).
Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients.
背景与目的。我们研究了50例接受非清髓性预处理后输注未处理或CD8细胞耗竭的异基因外周血干细胞患者的免疫恢复情况。
50例患者被随机分为两组，分别接受CD8细胞耗竭的外周血干细胞（n = 22）或未处理的外周血干细胞（n = 28）。患者的中位年龄为57岁（范围36 - 69岁）。预处理方案包括2 Gy全身照射，可加或不加氟达拉滨。20例患者接受来自相关供者的移植物，14例接受10/10 HLA等位基因匹配的无关供者的移植物，16例接受HLA不匹配的无关供者的移植物。移植物抗宿主病预防措施包括霉酚酸酯和环孢素。通过流式细胞术表型分析、TCRBV库多样性分析以及信号连接T细胞受体切除环（sjTREC）定量，评估造血细胞移植后第一年的免疫恢复情况。
移植物的CD8细胞耗竭降低了移植后前6个月CD8(+) T细胞计数的恢复（p < 0.0001），但对其他T细胞亚群的恢复无显著影响。在第100天至365天之间，sjTREC浓度和CD3(+) T细胞计数均显著增加（分别为p = 0.010和p = 0.0488），表明胸腺产生了新的T细胞。移植后1年与高sjTREC浓度相关的因素包括HLA匹配的无关供者（p = 0.029）、移植物中T细胞含量高（p = 0.002）以及无慢性移植物抗宿主病（p < 0.0001）。
我们的数据表明，在非清髓性移植后的最初几个月，免疫恢复主要由移植物中成熟T细胞的外周扩增驱动，而胸腺产生新的T细胞在移植患者的长期免疫重建中起重要作用。
