Gokmen E, Bachier C, Raaphorst F M, Muller T, Armstrong D, Lemaistre C F, Teale J M
The University of Texas Health Science Center, San Antonio, TX 78229, USA.
J Hematother Stem Cell Res. 2001 Feb;10(1):53-66. doi: 10.1089/152581601750098237.
The feasibility of using ex vivo-expanded hematopoietic progenitor cells to reconstitute hematopoiesis after high-dose chemotherapy is presently being examined. Early studies have shown that myeloid and erythroid hematopoiesis can be successfully reconstituted after high-dose chemotherapy and ex vivo-expanded hematopoietic cell transplantation. The lymphoid reconstitution, however, has not been addressed previously. In this study, we examined the diversity of the T cell receptor V beta chain (TCRBV) repertoires in 5 breast cancer patients who were transplanted with ex vivo-expanded bone marrow mononuclear cells as the only source of hematopoietic graft. Using the TCRBV third complementarity determining region (CDR3) fingerprinting methodology, it is shown that CD4(+) and CD8(+) T cell subsets after ex vivo-expanded hematopoietic cell graft transplants exhibit TCRBV diversities that are similar in complexity when compared to those seen after conventional autologous peripheral blood stem cell transplants (PBSCT). No apparent difference in the extent of CDR3 diversity was found between ex vivo expanded and conventional autologous PBSCT recipients when the CD4(+) and CD8(+) subsets were further separated into CD45RA(+) "naïve" and CD45RO(+) "memory" subsets. The diversity of the CD45RA(+) naïve subsets was as complex as that of the CD45RO(+) memory subsets. These results indicate that T cell repertoire diversification is not further compromised when ex vivo-expanded hematopoietic cells are used instead of autologous peripheral blood stem cells as the only source of graft.
目前正在研究使用体外扩增的造血祖细胞在大剂量化疗后重建造血功能的可行性。早期研究表明，大剂量化疗和体外扩增的造血细胞移植后，髓系和红系造血功能可以成功重建。然而，此前尚未涉及淋巴细胞重建。在本研究中，我们检测了5例乳腺癌患者的T细胞受体Vβ链（TCRBV）库的多样性，这些患者接受了体外扩增的骨髓单个核细胞作为唯一造血移植物来源的移植。使用TCRBV第三个互补决定区（CDR3）指纹图谱方法，结果显示，与传统自体外周血干细胞移植（PBSCT）后相比，体外扩增的造血细胞移植后的CD4(+)和CD8(+) T细胞亚群表现出相似复杂性的TCRBV多样性。当将CD4(+)和CD8(+)亚群进一步分为CD45RA(+)“幼稚”和CD45RO(+)“记忆”亚群时，体外扩增的和传统自体PBSCT受者之间在CDR3多样性程度上未发现明显差异。CD45RA(+)幼稚亚群的多样性与CD45RO(+)记忆亚群的多样性一样复杂。这些结果表明，当使用体外扩增的造血细胞代替自体外周血干细胞作为唯一移植物来源时，T细胞库的多样化不会进一步受损。
