Department of Internal Medicine I, Saarland University, Homburg, Germany.
Department of Internal Medicine IV, Saarland University, Homburg, Germany.
Eur J Haematol. 2018 Jul;101(1):38-47. doi: 10.1111/ejh.13077. Epub 2018 May 17.
As reconstitution of virus-specific T-cells is critical to control cytomegalovirus (CMV)-viremia following stem-cell transplantation (SCT), we characterized the dynamics in CMV-specific T-cell reconstitution after SCT.
Cytomegalovirus-specific T-cells from 51 SCT-recipients were prospectively quantified and phenotypically characterised by intracellular cytokine-staining after specific stimulation and HLA class-I-specific pentamers using flow cytometry.
Cytomegalovirus-specific CD4 T-cells reconstituted after a median of 2.3 (IQR, 2.0-3.0) weeks following autografting, and 4.0 (IQR, 3.0-5.6) weeks after allografting, with CMV-specific T-cells originating from donors and/or recipients. The time for reconstitution of CMV-specific CD4 and CD8 T-cells did not differ (P = .58). Factors delaying the time to initial reconstitution of CMV-specific CD4 T-cells included a negative recipient serostatus (P = .016) and CMV-viremia (P = .026). Percentages of CMV-specific CD4 T-cells significantly increased over time and reached a plateau after 90 days (P = .043). Relative CMV-specific CD4 T-cell levels remained higher in long-term transplant recipients compared with those in controls (P < .0001). However, due to persisting lymphopenia, absolute numbers of CMV-specific T-cells were similar as in controls.
Cytomegalovirus-specific T-cells rapidly reconstitute after SCT and their percentages remain high in the long term. In the face of persistent lymphopenia, this results in similar absolute numbers of CMV-specific T-cells as in controls to ensure sufficient pathogen control.
由于病毒特异性 T 细胞的重建对于控制干细胞移植(SCT)后巨细胞病毒(CMV)病毒血症至关重要,因此我们对 SCT 后 CMV 特异性 T 细胞重建的动态进行了特征描述。
通过使用流式细胞术对特定刺激后细胞内细胞因子染色和 HLA 类 I 特异性五聚体,对 51 例 SCT 受者的 CMV 特异性 T 细胞进行前瞻性定量和表型特征分析。
在自体移植后中位数为 2.3(IQR,2.0-3.0)周和同种异体移植后中位数为 4.0(IQR,3.0-5.6)周后,CMV 特异性 CD4 T 细胞得到重建,CMV 特异性 T 细胞来源于供体和/或受者。CMV 特异性 CD4 和 CD8 T 细胞重建的时间无差异(P=0.58)。延迟 CMV 特异性 CD4 T 细胞初始重建的因素包括受者血清学阴性(P=0.016)和 CMV 病毒血症(P=0.026)。CMV 特异性 CD4 T 细胞的百分比随时间显著增加,并在 90 天后达到平台期(P=0.043)。与对照组相比,长期移植受者的 CMV 特异性 CD4 T 细胞相对水平仍较高(P<0.0001)。然而,由于持续的淋巴细胞减少,CMV 特异性 T 细胞的绝对数量与对照组相似。
CMV 特异性 T 细胞在 SCT 后迅速重建,并且其百分比在长期内保持较高水平。在持续的淋巴细胞减少的情况下,这导致与对照组相似的 CMV 特异性 T 细胞的绝对数量,以确保足够的病原体控制。