Ritter J, Seitz V, Balzer H, Gary R, Lenze D, Moi S, Pasemann S, Seegebarth A, Wurdack M, Hennig S, Gerbitz A, Hummel M
Institute of Pathology, Charité - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
HS Diagnomics GmbH, Berlin, Germany.
Am J Transplant. 2015 Aug;15(8):2170-9. doi: 10.1111/ajt.13241. Epub 2015 Apr 14.
Delayed reconstitution of the T cell compartment in recipients of allogeneic stem cell grafts is associated with an increase of reactivation of latent viruses. Thereby, the transplanted T cell repertoire appears to be one of the factors that affect T cell reconstitution. Therefore, we studied the T cell receptor beta (TCRβ) gene rearrangements of flow cytometry-sorted CD4(+) and CD8(+) T cells from the peripheral blood of 23 allogeneic donors before G-CSF administration and on the day of apheresis. For this purpose, TCRβ rearrangements were amplified by multiplex PCR followed by high-throughput amplicon sequencing. Overall, CD4(+) T cells displayed a significantly higher TCRβ diversity compared to CD8(+) T cells irrespective of G-CSF administration. In line, no significant impact of G-CSF treatment on the TCR Vβ repertoire usage was found. However, correlation of the donor T cell repertoire with clinical outcomes of the recipient revealed that a higher CD4(+) TCRβ diversity after G-CSF treatment is associated with lower reactivation of cytomegalovirus and Epstein-Barr virus. By contrast, no protecting correlation was observed for CD8(+) T cells. In essence, our deep TCRβ analysis identifies the importance of the CD4(+) T cell compartment for the control of latent viruses after allogeneic stem cell transplantation.
同种异体干细胞移植受者的T细胞区室重建延迟与潜伏病毒再激活的增加有关。因此，移植的T细胞库似乎是影响T细胞重建的因素之一。因此，我们研究了23名同种异体供者在给予粒细胞集落刺激因子（G-CSF）之前及采集外周血干细胞当天，通过流式细胞术分选的外周血CD4(+)和CD8(+) T细胞的T细胞受体β（TCRβ）基因重排情况。为此，通过多重聚合酶链反应（PCR）扩增TCRβ重排，随后进行高通量扩增子测序。总体而言，无论是否给予G-CSF，CD4(+) T细胞的TCRβ多样性均显著高于CD8(+) T细胞。同样，未发现G-CSF治疗对TCR Vβ库使用有显著影响。然而，供者T细胞库与受者临床结局的相关性显示，G-CSF治疗后较高的CD4(+) TCRβ多样性与较低的巨细胞病毒和EB病毒再激活相关。相比之下，未观察到CD8(+) T细胞有保护相关性。本质上，我们深入的TCRβ分析确定了CD4(+) T细胞区室在同种异体干细胞移植后控制潜伏病毒方面的重要性。
