Kundu S K, Merigan T C
Center for AIDS Research, Stanford University, CA 94305.
Immunology. 1994 Sep;83(1):81-5.
The course of human immunodeficiency virus (HIV) infection progresses from an acute infection, through a prolonged asymptomatic phase, to an immunocompromised state. Some of the possible mechanisms underlying immune dysfunction include decreased HIV-specific cytotoxic T lymphocyte (CTL) activity, increased suppressor T cells, and/or increased HIV load. However, no study has been carried out to correlate all these factors. In this study, 26 patients showed > 3 log DNA copy number/10(6) CD4+ T cells, and seven patients had < 3 log DNA copy/10(6) CD4+ T cells. Patients with higher virus load had greater than 15% (19-45%) CD8+ CD11+ T cells. HIV-1 envelope-specific, HLA-restricted CTL activity (> 10%) was observed in 11 of 25 asymptomatic patients, and the remaining 14 patients lacked CTL activity (< 10%) in bulk assay. Although CTL activity was undetectable in these individuals, there was no significant difference in the frequency of activated CTL and their precursors in limiting dilution analysis. The patients with undetectable CTL activity had a higher percentage of CD8+ CD11+ T cells and a higher HIV-1 DNA copy number/million CD4+ T cells. Each of these parameters were significantly correlated with CD4+ T-cell numbers. The inverse relationship of CD8+ CD11+ T cells and virus load with HIV-specific CTL activity observed in this study may be one of the underlying factors which determines the course of HIV infection.
人类免疫缺陷病毒(HIV)感染的病程从急性感染开始,经过漫长的无症状期,发展到免疫功能受损状态。免疫功能障碍的一些潜在机制包括HIV特异性细胞毒性T淋巴细胞(CTL)活性降低、抑制性T细胞增加和/或HIV载量增加。然而,尚未进行研究来关联所有这些因素。在本研究中,26例患者的DNA拷贝数>3 log/10(6) CD4+ T细胞,7例患者的DNA拷贝数<3 log/10(6) CD4+ T细胞。病毒载量较高的患者有超过15%(19 - 45%)的CD8+ CD11+ T细胞。在25例无症状患者中,11例观察到HIV-1包膜特异性、HLA限制的CTL活性(>10%),其余14例患者在大量检测中缺乏CTL活性(<10%)。尽管在这些个体中检测不到CTL活性,但在有限稀释分析中,活化CTL及其前体的频率没有显著差异。CTL活性检测不到的患者CD8+ CD11+ T细胞百分比更高,HIV-1 DNA拷贝数/百万CD4+ T细胞也更高。这些参数中的每一个都与CD4+ T细胞数量显著相关。本研究中观察到的CD8+ CD11+ T细胞和病毒载量与HIV特异性CTL活性的负相关关系可能是决定HIV感染病程的潜在因素之一。