Godthelp B C, van Tol M J, Vossen J M, van den Elsen P J
Department of Pediatrics, Blood Bank, Leiden University Medical Centre, The Netherlands.
Hum Immunol. 1998 Apr;59(4):225-38. doi: 10.1016/s0198-8859(98)00013-5.
To evaluate the long-term reconstitution of the T cell immune repertoire in recipients of an allogeneic Bone Marrow Transplantation (allo-BMT), we have analyzed the T cell receptor (TCR) repertoire in the periphery and the T cell response against tetanus toxoid in two T- B+ Severe Combined Immunodeficiency Disease (SCID) patients more than 11 years after HLA haplo-identical allo-BMT. Our studies demonstrate that in the periphery of allo-BMT recipients, on the basis of TCR V-gene segment usage, the T cell immune repertoire long after allo-BMT is diverse, as is that of the donor. However, when donor and allo-BMT recipient were compared, differences were noted in the TCR Complementarity Determining Region 3 (CDR3) size distributions and in the T cell response against tetanus toxoid. In particular, the tetanus toxoid specific T cell clones differed in their use of HLA restriction elements, and expressed different T cell receptors. Moreover, we have uncovered donor-type tetanus toxoid specific T cell clones which were established from allo-BMT recipient derived peripheral blood lymphocytes and were found to be restricted by the non-shared recipient allele. This observation suggests a role for recipient-mediated T cell selection processes, in the thymus or at extra-thymic sites.
为了评估异基因骨髓移植（allo-BMT）受者T细胞免疫库的长期重建情况，我们分析了两名T⁺B⁺重症联合免疫缺陷病（SCID）患者在接受HLA单倍型相合allo-BMT超过11年后外周血中的T细胞受体（TCR）库以及针对破伤风类毒素的T细胞反应。我们的研究表明，在allo-BMT受者的外周血中，基于TCR V基因片段的使用情况，allo-BMT后很长时间的T细胞免疫库是多样的，与供者的免疫库一样。然而，当比较供者和allo-BMT受者时，发现TCR互补决定区3（CDR3）大小分布以及针对破伤风类毒素的T细胞反应存在差异。特别是，破伤风类毒素特异性T细胞克隆在HLA限制元件的使用上有所不同，并表达不同的T细胞受体。此外，我们发现了从allo-BMT受者外周血淋巴细胞中建立的供者型破伤风类毒素特异性T细胞克隆，这些克隆受非共享的受者等位基因限制。这一观察结果提示了受者介导的T细胞选择过程在胸腺或胸腺外部位所起的作用。
