Centre for Allogeneic Stem Cell Transplantation and Division of Clinical Immunology, Karolinska Institutet, Stockholm, Sweden.
Clin Exp Immunol. 2010 Oct;162(1):146-55. doi: 10.1111/j.1365-2249.2010.04212.x. Epub 2010 Aug 20.
Double cord blood transplantation (DCBT) with two matched or partially matched cord blood units has been implemented successfully to circumvent the limitations of graft cell dose associated with single CBT. After DCBT, sustained haematopoiesis is derived almost exclusively from only one of the donated units. None the less, we previously observed two of six evaluable DCBT patients still having mixed donor-donor chimerism at 28 and 45 months post-transplantation, respectively. In the present study we utilize flow cytometry techniques to perform the first thorough analysis of phenotype and functionality of cord blood units in patients with mixed donor-donor chimerism. Our results suggest that the two stable cord blood units are different phenotypically and functionally: one unit shows more naive T cells, lower T cell cytokine production and higher frequencies of natural killer cells, the other shows higher frequencies of well-differentiated and functional lymphocytes. Additionally, in comparison with control patients having a single prevailing cord blood unit, the patients with donor-donor chimerism exhibit less overall T cell cytokine production and a smaller fraction of memory T cells. Furthermore, our results indicate that human leucocyte antigen-C match of donor units may partly explain the development of a donor-donor mixed chimerism.
双份脐带血移植(DCBT)采用两个匹配或部分匹配的脐带血单位,成功地规避了与单个 CBT 相关的移植物细胞剂量的限制。在 DCBT 之后,持续的造血几乎完全来自于捐赠的单位之一。尽管如此,我们之前观察到 6 名可评估的 DCBT 患者中的 2 名,分别在移植后 28 个月和 45 个月时仍存在混合供体-供体嵌合体。在本研究中,我们利用流式细胞术技术对混合供体-供体嵌合体患者的脐带血细胞表型和功能进行了首次全面分析。我们的结果表明,两个稳定的脐带血单位在表型和功能上存在差异:一个单位显示出更多的幼稚 T 细胞、较低的 T 细胞细胞因子产生和较高的自然杀伤细胞频率,另一个单位显示出更高频率的分化良好和功能齐全的淋巴细胞。此外,与具有单个主要脐带血单位的对照患者相比,嵌合体患者的整体 T 细胞细胞因子产生较少,记忆 T 细胞比例较小。此外,我们的结果表明,供体单位的人类白细胞抗原-C 匹配可能部分解释了供体-供体混合嵌合体的发展。