Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Biol Blood Marrow Transplant. 2019 Mar;25(3):417-423. doi: 10.1016/j.bbmt.2018.10.012. Epub 2018 Oct 22.
Owing to the difficulty in isolating T cells from human biopsy samples, the characteristics of T cells that are infiltratinghuman acute graft-versus-host disease (GVHD) tissues remain largely uninvestigated. In the present study, TCR-β deep sequencing of various GVHD tissue samples and concurrent peripheral blood obtained from transplant recipients was performed in combination with functional assays of tissue-infiltrating T cell clones. The T cell repertoire was more skewed in GVHD tissues than in the peripheral blood. The frequent clonotypes differed from tissue to tissue in the same patient, and the frequent clonotypes in the same tissue differed from patient to patient. Two T cell clones were successfully isolated from GVHD skin of a patient. In a cytotoxicity assay, both Tcell clones lysed patient peripheral blood mononuclear cells, but not donor-derived Epstein-Barr virus-transformed lymphoblastoid cells. Their clonotypes were identical to the most and second most frequent T cell clonotypes in the original GVHD skin and accounted for almost all of the skin-infiltrating T cells. These results suggest that human acute GVHD may result from only a few different alloreactive cytotoxic T cell clones, which differ from tissue to tissue and from patient to patient. The characterization of T cells infiltrating human GVHD tissues should be further investigated.
由于从人类活检样本中分离 T 细胞存在困难，浸润人类急性移植物抗宿主病 (GVHD) 组织的 T 细胞特征在很大程度上仍未得到研究。在本研究中，对移植受者的各种 GVHD 组织样本和同时获得的外周血进行了 TCR-β 深度测序，并结合组织浸润 T 细胞克隆的功能测定。与外周血相比，GVHD 组织中的 T 细胞库更为偏倚。同一患者同一组织的频繁克隆型不同，同一组织的频繁克隆型也因患者而异。从一名患者的 GVHD 皮肤中成功分离出两个 T 细胞克隆。在细胞毒性测定中，两个 T 细胞克隆均溶解患者外周血单个核细胞，但不溶解供体来源的 Epstein-Barr 病毒转化的淋巴母细胞系。它们的克隆型与原始 GVHD 皮肤中最频繁和第二频繁的 T 细胞克隆型相同，几乎占所有皮肤浸润 T 细胞。这些结果表明，人类急性 GVHD 可能仅由少数不同的同种反应性细胞毒性 T 细胞克隆引起，这些克隆型在组织间和患者间存在差异。浸润人类 GVHD 组织的 T 细胞的特征应进一步研究。
