Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Department of Microbiology and Immunology, Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, California, USA.
JCI Insight. 2021 Nov 8;6(21):e153175. doi: 10.1172/jci.insight.153175.
CMV causes mostly asymptomatic but lifelong infection. Primary infection or reactivation in immunocompromised individuals can be life-threatening. CMV viremia often occurs in solid organ transplant recipients and associates with decreased graft survival and higher mortality. Furthering understanding of impaired immunity that allows CMV reactivation is critical to guiding antiviral therapy and examining the effect of CMV on solid organ transplant outcomes. This study characterized longitudinal immune responses to CMV in 31 kidney transplant recipients with CMV viremia and matched, nonviremic recipients. Recipients were sampled 3 and 12 months after transplant, with additional samples 1 week and 1 month after viremia. PBMCs were stained for NK and T cell markers. PBMC transcriptomes were characterized by RNA-Seq. Plasma proteins were quantified by Luminex. CD8+ T cell transcriptomes were characterized by single-cell RNA-Seq. Before viremia, patients had high levels of IL-15 with concurrent expansion of immature CD56bright NK cells. After viremia, mature CD56dim NK cells and CD28-CD8+ T cells upregulating inhibitory and NK-associated receptors were expanded. Memory NK cells and NK-like CD28-CD8+ T cells were associated with control of viremia. These findings suggest that signatures of innate activation may be prognostic for CMV reactivation after transplant, while CD8+ T cell functionality is critical for effective control of CMV.
CMV 主要引起无症状但终身感染。免疫功能低下者的原发感染或再激活可能危及生命。CMV 病毒血症常发生于实体器官移植受者，与移植物存活率降低和死亡率升高相关。深入了解导致 CMV 再激活的免疫功能受损对于指导抗病毒治疗和研究 CMV 对实体器官移植结局的影响至关重要。本研究对 31 例 CMV 病毒血症的肾移植受者和匹配的非病毒血症受者进行了 CMV 纵向免疫应答特征分析。受者在移植后 3 个月和 12 个月接受采样，并在病毒血症后 1 周和 1 个月进行额外采样。PBMC 用 NK 和 T 细胞标志物进行染色。通过 RNA-Seq 对 PBMC 转录组进行特征分析。通过 Luminex 定量测定血浆蛋白。通过单细胞 RNA-Seq 对 CD8+T 细胞转录组进行特征分析。在病毒血症之前，患者具有高水平的 IL-15，并伴有不成熟的 CD56bright NK 细胞的同时扩增。病毒血症后，成熟的 CD56dim NK 细胞和 CD28-CD8+T 细胞上调抑制性和 NK 相关受体而扩增。记忆 NK 细胞和 NK 样 CD28-CD8+T 细胞与控制病毒血症相关。这些发现表明，固有激活的特征可能是移植后 CMV 再激活的预后指标，而 CD8+T 细胞功能对于 CMV 的有效控制至关重要。
