Martín-Donaire T, Rico M, Bautista G, Gonzalo-Daganzo R, Regidor C, Ojeda E, Sanjuán I, Forés R, Ruiz E, Krsnik I, Navarro B, Gil S, Magro E, Millán I, Sánchez R, Pérez-Sanz N, Panadero N, García-Marco J A, Cabrera R, Fernández M N
Department of Hematology, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Madrid, Spain.
Bone Marrow Transplant. 2009 Aug;44(4):213-25. doi: 10.1038/bmt.2009.15. Epub 2009 Mar 2.
Low severity of GVHD, substantial graft vs tumor (GVT) and slow development of protective immunity are well-documented features of cord blood transplants (CBT). We have evaluated the immune reconstitution of adult recipients of single-unit CBT supported by the coinfusion of third party donor (TPD) mobilized hematopoietic stem cells (MHSC), a procedure-'dual CB/TPD-MHSC transplant'-that results in early recovery of circulating granulocytes, high rates of CB engraftment and full chimerism. Cumulative recovery of natural killer and B cells at or above the median values of normal controls were 1.0 and 0.76 by the sixth and ninth months. Recovery of T cells was much slower, naive cells lagging behind those of memory and effector (committed) immunophenotypes. Serial analyses of signal joint TCR excision circles showed a general pattern of very low levels by the third month after CBT, followed by recovery to levels persistently similar or higher than those observed before transplantation and in normal controls. Our results are consistent with the clinical observations of substantial GVT effect together with low incidence of serious GVHD and slow development of protective immunity and suggest that thymic function contributes substantially to the recovery of T-cell populations in adults receiving dual CB/TPD-MHSC transplants.
移植物抗宿主病（GVHD）严重程度低、显著的移植物抗肿瘤效应（GVT）以及保护性免疫反应发展缓慢，都是脐血移植（CBT）中充分记录的特征。我们评估了接受单单位CBT的成年受者的免疫重建情况，这些受者同时输注第三方供体（TPD）动员的造血干细胞（MHSC），这一过程——“双份脐血/TPD-MHSC移植”——可使循环粒细胞早期恢复、脐血植入率高且实现完全嵌合。到第六个月和第九个月时，自然杀伤细胞和B细胞的累积恢复率达到或高于正常对照中位数的比例分别为1.0和0.76。T细胞的恢复要慢得多，幼稚细胞落后于记忆细胞和效应（定向）免疫表型的细胞。对信号接头TCR切除环的系列分析显示，CBT后第三个月时一般水平很低，随后恢复到持续与移植前及正常对照中观察到的水平相似或更高的水平。我们的结果与GVT效应显著、严重GVHD发生率低以及保护性免疫反应发展缓慢的临床观察结果一致，并表明胸腺功能对接受双份脐血/TPD-MHSC移植的成年人T细胞群体的恢复有很大贡献。
