Borysiewicz L K, Graham S, Hickling J K, Mason P D, Sissons J G
Department of Medicine, Royal Postgraduate Medical School, London, GB.
Eur J Immunol. 1988 Feb;18(2):269-75. doi: 10.1002/eji.1830180214.
Human virus-specific cytotoxic T (Tc) cells may be important in maintaining the virus/host equilibrium during persistent herpes virus infections such as that with human cytomegalovirus (HCMV). We have previously shown that HCMV-specific Tc cells are present in peripheral blood in normal asymptomatic seropositive individuals (L. K. Borysiewicz et al., Eur. J. Immunol. 1983. 13: 804). In this study we have used limiting dilution analysis to estimate the precursor frequency of these Tc cells and to further delineate their specificity for viral proteins expressed at different stages of the virus replicative cycle. HCMV-specific Tc precursor cells were present in peripheral blood lymphocytes (PBL) at a frequency of 1/5000 to 20,000 E+ PBL. This frequency was higher than that observed for varicella-zoster virus (VZV)-specific Tc cells (1/30,000 to greater than 500,000) in asymptomatic individuals and was similar to the VZV Tc precursor cell frequencies observed following clinical reactivation (1/30,000). When the stage specificity of clonally derived HCMV-specific Tc cells was analyzed, using target cells treated with phosphonoformate to allow expression of only the nonstructural viral proteins, the majority (60%) of Tc cells lysed these cells. A number of Tc cells lysed only cells which expressed the structural or late HCMV proteins. These results suggest a high precursor frequency of HCMV-specific Tc cells in PBL, and that there are subpopulations of such Tc cells specific for HCMV antigens expressed at different stages of the virus replicative cycle. However, the relative frequencies of these subpopulations suggest that the immunodominant HCMV antigens with respect to the Tc response are expressed at immediate early and/or early times.
在持续性疱疹病毒感染（如人巨细胞病毒，HCMV）期间，人类病毒特异性细胞毒性T（Tc）细胞对于维持病毒/宿主平衡可能至关重要。我们之前已经表明，在正常无症状血清阳性个体的外周血中存在HCMV特异性Tc细胞（L. K. 博里谢维茨等人，《欧洲免疫学杂志》，1983年。13: 804）。在本研究中，我们使用有限稀释分析来估计这些Tc细胞的前体细胞频率，并进一步描绘它们对病毒复制周期不同阶段表达的病毒蛋白的特异性。HCMV特异性Tc前体细胞在外周血淋巴细胞（PBL）中的频率为1/5000至20,000个E+ PBL。这个频率高于无症状个体中水痘带状疱疹病毒（VZV）特异性Tc细胞的频率（1/30,000至大于500,000），并且与临床再激活后观察到的VZV Tc前体细胞频率（1/30,000）相似。当使用经膦甲酸处理以仅允许非结构病毒蛋白表达的靶细胞来分析克隆衍生的HCMV特异性Tc细胞的阶段特异性时，大多数（60%）Tc细胞裂解了这些细胞。一些Tc细胞仅裂解表达结构或晚期HCMV蛋白的细胞。这些结果表明PBL中HCMV特异性Tc细胞的前体细胞频率很高，并且存在针对病毒复制周期不同阶段表达的HCMV抗原特异性的此类Tc细胞亚群。然而，这些亚群的相对频率表明，相对于Tc反应的免疫显性HCMV抗原在立即早期和/或早期表达。
