Gillespie G M, Wills M R, Appay V, O'Callaghan C, Murphy M, Smith N, Sissons P, Rowland-Jones S, Bell J I, Moss P A
MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
J Virol. 2000 Sep;74(17):8140-50. doi: 10.1128/jvi.74.17.8140-8150.2000.
Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8(+) T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8(+) T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in "fresh" killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.
人巨细胞病毒（HCMV）感染在免疫功能正常的宿主中大多无症状，但仍是免疫抑制个体发病的主要原因。利用最近描述的用肽-HLA四聚体复合物对抗原特异性CD8(+) T细胞进行染色的技术，我们已证明存在高水平的针对HCMV肽的抗原特异性细胞，并表明在免疫功能正常的供体中，这一比例可能超过CD8(+) T细胞的4%。此外，通过用四聚体与细胞表面标志物抗体和细胞内细胞因子抗体联合染色，我们证明了HCMV特异性群体的功能异质性。其中很大一部分是效应性细胞毒性T淋巴细胞，这在“新鲜”杀伤试验中通过它们裂解肽脉冲靶标的能力得以证明。这些数据表明，对HCMV的免疫反应会因低水平的HCMV复制而周期性增强，持续的免疫监视有助于维持宿主-病原体的稳态。这些观察结果应能增进我们对持续性病毒感染免疫生物学的理解。
