Pourgheysari B, Piper K P, McLarnon A, Arrazi J, Bruton R, Clark F, Cook M, Mahendra P, Craddock C, Moss P A H
CRUK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
Bone Marrow Transplant. 2009 Jun;43(11):853-61. doi: 10.1038/bmt.2008.403. Epub 2008 Dec 22.
Reactivation of CMV is a common complication following allogeneic haematopoietic SCT and is associated with significant morbidity and mortality. The relative importance of the CD4+ and CD8+ components of the CMV-specific immune response in protection from reactivation is unclear. The CMV-specific CD4+ and CD8+ immune response was measured at serial time points in 32 patients following allogeneic HSCT. Intracellular cytokine staining following CMV lysate stimulation and HLA-peptide tetramers were used to determine CMV-specific CD4+ and CD8+ responses, respectively. A deficient CMV-specific CD4+ T-cell immune response within the first 30-50 days post transplant was associated with high risk of viral reactivation. Patients with combined impairment of the CD4+ and CD8+ immune response within the first 100 days were susceptible to late viral reactivation. The frequency of CMV-specific CD4+ T cells correlated with CMV-specific CD8+ T cells, comprising 10% of the whole T-cell repertoire. Early CMV-specific CD4+ T-cell reconstitution was dominated by effector memory cells with normal levels of IL-2 resuming 6 months following transplantation. In summary, both CD4 and CD8 CMV-specific immune reconstitution is required for protection from recurrent activation. Measurement of the magnitude of the CMV-specific CD4+ immune response is useful in managing viral reactivation following HSCT.
巨细胞病毒（CMV）再激活是异基因造血干细胞移植（SCT）后常见的并发症，与显著的发病率和死亡率相关。CMV特异性免疫反应中CD4⁺和CD8⁺成分在预防再激活中的相对重要性尚不清楚。在32例异基因造血干细胞移植（HSCT）后的患者中，在多个时间点测量了CMV特异性免疫反应。分别使用CMV裂解物刺激后的细胞内细胞因子染色和HLA肽四聚体来确定CMV特异性CD4⁺和CD8⁺反应。移植后最初30 - 50天内CMV特异性CD4⁺T细胞免疫反应缺陷与病毒再激活的高风险相关。在最初100天内CD4⁺和CD8⁺免疫反应联合受损的患者易发生晚期病毒再激活。CMV特异性CD4⁺T细胞的频率与CMV特异性CD8⁺T细胞相关，占整个T细胞库的10%。早期CMV特异性CD4⁺T细胞重建以效应记忆细胞为主，移植后6个月白细胞介素-2水平恢复正常。总之，CD4和CD8的CMV特异性免疫重建对于预防复发性激活都是必需的。测量CMV特异性CD4⁺免疫反应的强度有助于管理HSCT后的病毒再激活。
