Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
Division of Infectious Disease, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Exp Mol Med. 2017 Sep 29;49(9):e382. doi: 10.1038/emm.2017.146.
Human cytomegalovirus (HCMV) establishes a lifelong chronic latent infection and often reactivates in immunocompromised patients. In addition, HCMV reactivates in patients with sepsis or other critical illnesses, particularly in patients with poor prognoses. However, the immunological characteristics of sepsis patients with HCMV reactivation have not been elucidated. In the present study, we examined T-cell responses in severe sepsis patients with and without HCMV reactivation. First, HCMV pp65-specific T-cell functions were assessed by intracellular cytokine staining (ICS) for IFN-γ, TNF-α, and MIP-1β and by CD107a staining. We analyzed the ICS data for each function individually and found no difference between the patient groups. However, the relative frequency of polyfunctional CD8 T cells was significantly decreased in sepsis patients with HCMV reactivation. Next, we examined programmed cell death protein 1 (PD-1) expression. It was significantly increased in the CD8 T-cell population in severe sepsis patients with HCMV reactivation, indicating CD8 T-cell exhaustion. Interestingly, the frequency of PD-1 cells in the CD8 T-cell population was inversely correlated with the relative frequency of polyfunctional CD8 T cells. Herein, we demonstrate that HCMV reactivation in severe sepsis patients is associated with PD-1 expression and impaired polyfunctionality of CD8 T cells.
人巨细胞病毒（HCMV）建立终身慢性潜伏感染，常在免疫功能低下的患者中重新激活。此外，HCMV 在脓毒症或其他危重病患者中重新激活，特别是在预后不良的患者中。然而，HCMV 重新激活的脓毒症患者的免疫学特征尚未阐明。在本研究中，我们研究了伴有和不伴有 HCMV 重新激活的严重脓毒症患者的 T 细胞反应。首先，通过细胞内细胞因子染色（ICS）检测 IFN-γ、TNF-α 和 MIP-1β以及 CD107a 染色来评估 HCMV pp65 特异性 T 细胞功能。我们分别分析了每个功能的 ICS 数据，未发现两组患者之间存在差异。然而，HCMV 重新激活的脓毒症患者中多能性 CD8 T 细胞的相对频率显著降低。接下来，我们研究了程序性死亡蛋白 1（PD-1）的表达。在伴有 HCMV 重新激活的严重脓毒症患者的 CD8 T 细胞群体中，PD-1 的表达显著增加，表明 CD8 T 细胞衰竭。有趣的是，CD8 T 细胞群体中 PD-1 细胞的频率与多能性 CD8 T 细胞的相对频率呈负相关。本研究表明，严重脓毒症患者的 HCMV 重新激活与 PD-1 表达和 CD8 T 细胞的多功能性受损有关。
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