Wang E C, Moss P A, Frodsham P, Lehner P J, Bell J I, Borysiewicz L K
Department of Medicine, University of Wales College of Medicine, Health Hospital, Cardiff, United Kingdom.
J Immunol. 1995 Nov 15;155(10):5046-56.
CD8+CD57+ lymphocytes from normal peripheral blood are divided into T cells expressing high levels of CD8 and NK cells expressing low levels of surface CD8. Increased numbers of CD8highCD57+ T cells correlate with previous exposure to human cytomegalovirus (HCMV) infection, but no virus-specific function or function for CD8highCD57+ cells has been recorded. We have studied the TCR repertoire and responses of the CD8highCD57+ population induced by virus-infected fibroblasts in healthy individuals. Using three-color flow cytometry of PBL, we detected restricted TCRBV usage in the CD8highCD57+ subset of 11/15 subjects, compared with 1/15 in the CD8+, CD57- subset. The results of anchored PCR and sequencing also showed oligoclonality of TCR; 40-70% of CD8highCD57+ lymphocytes (10-20% of total CD8+ T cells) were derived from single clones. Such expansions were stable with time and detected in one subject over a 2-yr period. Functionally, CD8highCD57+ lymphocytes proliferated strongly to HCMV-, but not HSV-, VZV-, or influenza-infected fibroblasts in an MHC-unrestricted manner in vitro, including preferential augmentation of particular in vivo oligoclonally expanded subpopulations. HCMV-specific MHC-restricted CTL were detected, but limiting dilution analysis showed that these were a minority (< 10%) and not the oligoclonal subsets. In contrast, depletion of oligoclonally expanded CD8highCD57+ subpopulations, resulted in the increase of HCMV-specific CTL, suggesting functional heterogeneity in these cells.
正常外周血中的CD8⁺CD57⁺淋巴细胞可分为高表达CD8的T细胞和低表达表面CD8的NK细胞。CD8高表达CD57⁺T细胞数量的增加与既往人类巨细胞病毒（HCMV）感染相关，但尚未记录到CD8高表达CD57⁺细胞的病毒特异性功能或功能情况。我们研究了健康个体中病毒感染的成纤维细胞诱导的CD8高表达CD57⁺群体的TCR库和反应。通过对外周血淋巴细胞进行三色流式细胞术检测，我们发现11/15名受试者的CD8高表达CD57⁺亚群中TCRBV使用受限，而CD8⁺、CD57⁻亚群中只有1/15名受试者如此。锚定PCR和测序结果也显示TCR呈寡克隆性；40 - 70%的CD8高表达CD57⁺淋巴细胞（占总CD8⁺T细胞的10 - 20%）来源于单个克隆。这种扩增随时间稳定，在一名受试者中持续检测了2年。在功能上，CD8高表达CD57⁺淋巴细胞在体外以MHC非限制性方式对HCMV感染的成纤维细胞有强烈增殖反应，但对HSV、VZV或流感感染的成纤维细胞无反应，包括体内特定寡克隆扩增亚群的优先增加。检测到HCMV特异性MHC限制性CTL，但有限稀释分析表明这些是少数（<10%），并非寡克隆亚群。相反，寡克隆扩增的CD8高表达CD57⁺亚群的耗竭导致HCMV特异性CTL增加，提示这些细胞存在功能异质性。
