Moss P A, Rowland-Jones S L, Frodsham P M, McAdam S, Giangrande P, McMichael A J, Bell J I
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5773-7. doi: 10.1073/pnas.92.13.5773.
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（HIV）特异性细胞毒性T淋巴细胞（CTL）被认为在针对HIV感染的免疫反应中起主要作用。HIV特异性CTL反应比之前在一种传染病中所记录的要强得多，然而，通过有限稀释分析（LDA）得出的CTL频率估计值相对较低，与其他病毒感染相当。在这里，我们表明，在三名受感染患者的外周血中，针对HIV gag和pol基因产物肽段的单个CTL克隆水平很高，并且单个CTL克隆可能占T细胞的0.2%至1%。之前对一名供体进行的LDA显示CTL前体频率为1/8000，这表明LDA可能低估了CTL效应频率。在一些供体中，单个CTL克隆在体内持续存在至少5年。相比之下，在一名患者中，CTL使用情况发生了转变，这表明在感染过程中可以招募不同群体的CTL。这些数据意味着CTL受到强烈刺激，可能导致一些克隆耗竭。
