Drylewicz Julia, Schellens Ingrid M M, Gaiser Rogier, Nanlohy Nening M, Quakkelaar Esther D, Otten Henny, van Dorp Suzanne, Jacobi Ronald, Ran Leonie, Spijkers Sanne, Koning Dan, Schuurman Rob, Meijer Ellen, Pietersma Floortje L, Kuball Jurgen, van Baarle Debbie
Laboratory of Translational Immunology, Department of Immunology, Utrecht, The Netherlands.
Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Utrecht, The Netherlands.
J Transl Med. 2016 Aug 2;14(1):230. doi: 10.1186/s12967-016-0988-4.
Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT).
Here we investigated the role of immune cell reconstitution in the onset and subsequent severity of EBV- and CMV-reactivation. To this end, 116 patients were prospectively sampled for absolute T cell (CD4 and CD8), B-cell (CD19) and NK-cell (CD16 and CD56) numbers weekly post-SCT during the first 3 months and thereafter monthly until 6 months post-SCT. Viral load was monitored in parallel.
In contrast to the general belief, we found that early T-cell reconstitution does not play a role in the onset of viral reactivation. CMV reactivation in the first 7 weeks after SCT however resulted in higher absolute CD8(+) T-cell numbers 6 months post-SCT in patients with high-level reactivation, many of which were CMV-specific. Interestingly, rapid reconstitution of CD4(+) T-cells, as well as NK cells and the presence of donor KIR3DL1, are associated with the absence of CMV-reactivation after SCT, suggestive of a protective role of these cells. In contrast, EBV-reactivations were not affected in any way by the level of immune reconstitution after SCT.
In conclusion, these data suggest that CD4(+) T-cells and NK cells, rather than CD8(+) T-cells, are associated with protection against CMV-reactivation.
爱泼斯坦-巴尔病毒和巨细胞病毒再激活在异基因干细胞移植(SCT)后频繁发生。
在此,我们研究了免疫细胞重建在EBV和CMV再激活的发生及后续严重程度中的作用。为此,前瞻性地对116例患者进行采样,在SCT后的前3个月每周检测绝对T细胞(CD4和CD8)、B细胞(CD19)和NK细胞(CD16和CD56)数量,此后每月检测直至SCT后6个月。同时监测病毒载量。
与普遍看法相反,我们发现早期T细胞重建在病毒再激活的发生中不起作用。然而,SCT后前7周的CMV再激活导致高再激活水平患者在SCT后6个月时绝对CD8(+) T细胞数量增加,其中许多是CMV特异性的。有趣的是,CD4(+) T细胞以及NK细胞的快速重建和供体KIR3DL1的存在与SCT后无CMV再激活相关,提示这些细胞具有保护作用。相比之下,SCT后免疫重建水平对EBV再激活没有任何影响。
总之,这些数据表明,CD4(+) T细胞和NK细胞而非CD8(+) T细胞与预防CMV再激活有关。