Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTLs) are thought to play a major role in the immune response to HIV infection. The HIV-specific CTL response is much stronger than previously documented in an infectious disease, yet estimates of CTL frequency derived from limiting-dilution analysis (LDA) are relatively low and comparable to other viral infections. Here we show that individual CTL clones specific for peptides from HIV gag and pol gene products are present at high levels in the peripheral blood of three infected patients and that individual CTL clones may represent between 0.2% and 1% of T cells. Previous LDA in one donor had shown a frequency of CTL precursors of 1/8000, suggesting that LDA may underestimate CTL effector frequency. In some donors individual CTL clones persisted in vivo for at least 5 years. In contrast, in one patient there was a switch in CTL usage suggesting that different populations of CTLs can be recruited during infection. These data imply strong stimulation of CTLs, potentially leading some clones to exhaustion.

人类免疫缺陷病毒（Human immunodeficiency virus, HIV）特异性细胞毒性T淋巴细胞（cytotoxic T lymphocytes, CTLs）被认为在HIV感染的免疫应答中发挥主要作用。相较于此前在传染病中记录的水平，HIV特异性CTL应答的强度要高出许多，但通过有限稀释分析法（limiting-dilution analysis, LDA）得到的CTL频率估算值却相对偏低，与其他病毒感染的估算值不相上下。本研究显示，3名HIV感染患者的外周血中存在针对HIV gag与pol基因产物来源肽段的单个CTL克隆，且单个CTL克隆可占T细胞总数的0.2%至1%。此前针对1名供体开展的LDA检测显示，其CTL前体细胞频率为1/8000，这提示LDA可能低估了CTL效应细胞的实际频率。部分供体体内的单个CTL克隆可在体内存活至少5年。与之相反，1名患者的CTL识别谱出现了转换，表明感染过程中可招募不同群体的CTL。上述数据提示CTL受到了强烈的抗原刺激，这可能导致部分克隆出现耗竭。