Division of Infectious Diseases, Department of Medicine, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom.
Front Cell Infect Microbiol. 2020 May 19;10:202. doi: 10.3389/fcimb.2020.00202. eCollection 2020.
While CD8+ T cells specific for human cytomegalovirus (HCMV) have been extensively studied in both healthy HCMV seropositive carriers and patients undergoing immunosuppression, studies on the CD4+ T cell response to HCMV had lagged behind. However, over the last few years there has been a significant advance in our understanding of the importance and contribution that CMV-specific CD4+ T cells make, not only to anti-viral immunity but also in the potential maintenance of latently infected cells. During primary infection with HCMV in adults, CD4+ T cells are important for the resolution of symptomatic disease, while persistent shedding of HCMV into urine and saliva is associated with a lack of HCMV specific CD4+ T cell response in young children. In immunosuppressed solid organ transplant recipients, a delayed appearance of HCMV-specific CD4+ T cells is associated with prolonged viremia and more severe clinical disease, while in haematopoietic stem cell transplant recipients, it has been suggested that HCMV-specific CD4+ T cells are required for HCMV-specific CD8+ T cells to exert their anti-viral effects. In addition, adoptive T-cell immunotherapy in transplant patients has shown that the presence of HCMV-specific CD4+ T cells is required for the maintenance of HCMV-specific CD8+ T cells. HCMV is a paradigm for immune evasion. The presence of viral genes that down-regulate MHC class II molecules and the expression of viral IL-10 both limit antigen presentation to CD4+ T cells, underlining the important role that this T cell subset has in antiviral immunity. This review will discuss the antigen specificity, effector function, phenotype and direct anti-viral properties of HCMV specific CD4+ T cells, as well as reviewing our understanding of the importance of this T cell subset in primary infection and long-term carriage in healthy individuals. In addition, their role and importance in congenital HCMV infection and during immunosuppression in both solid organ and haemopoietic stem cell transplantation is considered.
虽然针对人类巨细胞病毒（HCMV）的 CD8+ T 细胞在健康的 HCMV 血清阳性携带者和接受免疫抑制治疗的患者中已经得到了广泛研究，但对 HCMV 的 CD4+ T 细胞反应的研究却落后了。然而，在过去的几年中，我们对 CMV 特异性 CD4+ T 细胞的重要性和贡献有了更深入的理解，这些细胞不仅对抗病毒免疫有重要作用，而且对潜伏感染细胞的维持也有潜在作用。在成人初次感染 HCMV 时，CD4+ T 细胞对于缓解症状性疾病很重要，而年幼儿童缺乏 HCMV 特异性 CD4+ T 细胞反应与 HCMV 持续从尿液和唾液中排出有关。在免疫抑制的实体器官移植受者中，HCMV 特异性 CD4+ T 细胞出现延迟与病毒血症持续时间延长和更严重的临床疾病有关，而在造血干细胞移植受者中，有人认为 HCMV 特异性 CD4+ T 细胞对于 HCMV 特异性 CD8+ T 细胞发挥抗病毒作用是必需的。此外，在移植患者中进行的过继性 T 细胞免疫疗法表明，HCMV 特异性 CD4+ T 细胞的存在对于维持 HCMV 特异性 CD8+ T 细胞是必需的。HCMV 是免疫逃避的典范。病毒基因下调 MHC Ⅱ类分子的表达和病毒 IL-10 的表达都限制了抗原呈递给 CD4+ T 细胞，这突出了该 T 细胞亚群在抗病毒免疫中的重要作用。这篇综述将讨论 HCMV 特异性 CD4+ T 细胞的抗原特异性、效应功能、表型和直接抗病毒特性，并回顾我们对该 T 细胞亚群在健康个体初次感染和长期携带中的重要性的理解。此外，还考虑了它们在先天性 HCMV 感染和实体器官及造血干细胞移植中免疫抑制期间的作用和重要性。
