Allen J B, McCartney-Francis N, Smith P D, Simon G, Gartner S, Wahl L M, Popovic M, Wahl S M
Cellular Immunology Section, NIDR, Bethesda, Maryland 20892.
J Clin Invest. 1990 Jan;85(1):192-9. doi: 10.1172/JCI114412.
A population of circulating mononuclear cells from patients with AIDS was identified which expressed interleukin 2 receptors (IL-2R). By dual-fluorescence flow microfluorometry, the patients' IL-2R+ cells were further identified as Leu M3+ monocytes (29.4 +/- 5.2% of the Leu M3+ cells were IL-2R+, n = 15), whereas Leu M3+ monocytes from normal subjects were IL-2R negative (2.0 +/- 0.42%; P less than 0.001). By Northern analysis, monocytes from AIDS patients, but not control subjects, constitutively expressed steady-state levels of IL-2R mRNA. Functionally, the IL-2R+ monocytes were capable of depleting IL-2 from culture supernatants, suggesting a mechanism for the reduced IL-2 levels commonly seen in AIDS patients. IL-2R+ monocytes also expressed increased levels of surface HLA-DR which may favor monocyte T-cell interactions and the transmission of human immunodeficiency virus (HIV). In additional studies, normal monocytes were infected with a macrophage-tropic HIV isolate in vitro and monitored for IL-2R and HLA-DR expression. Within 24-48 h after exposure to HIV in vitro, but before evidence of productive infection, greater than 25% of the monocytes became IL-2R+ with increasing numbers of IL-2R+ cells and HLA-DR levels through day 6. These early signaling effects of HIV could be mimicked by adding purified HIV envelope glycoprotein gp120 to the monocytes. This stimulation of monocytes before or independent of productive infection of the cells by HIV is consistent with in vivo observations of activated and/or abnormal functions by monocytes that do not appear to be infected with HIV in AIDS patients.
已鉴定出艾滋病患者循环单核细胞群体表达白细胞介素2受体(IL-2R)。通过双荧光流式微量荧光测定法,患者的IL-2R+细胞进一步被鉴定为Leu M3+单核细胞(Leu M3+细胞的29.4±5.2%为IL-2R+,n = 15),而正常受试者的Leu M3+单核细胞为IL-2R阴性(2.0±0.42%;P<0.001)。通过Northern分析,艾滋病患者的单核细胞而非对照受试者的单核细胞组成性地表达IL-2R mRNA的稳态水平。在功能上,IL-2R+单核细胞能够从培养上清液中消耗IL-2,提示了艾滋病患者中常见的IL-2水平降低的一种机制。IL-2R+单核细胞还表达增加的表面HLA-DR水平,这可能有利于单核细胞与T细胞相互作用以及人类免疫缺陷病毒(HIV)的传播。在另外的研究中,正常单核细胞在体外被巨噬细胞嗜性HIV分离株感染,并监测IL-2R和HLA-DR表达。在体外暴露于HIV后24 - 48小时内,但在有 productive感染证据之前,超过25%的单核细胞变为IL-2R+,到第6天时IL-2R+细胞数量和HLA-DR水平不断增加。HIV的这些早期信号作用可通过向单核细胞中添加纯化的HIV包膜糖蛋白gp120来模拟。在HIV对细胞进行 productive感染之前或独立于此的情况下对单核细胞的这种刺激与艾滋病患者体内未被HIV感染的单核细胞的活化和/或异常功能的观察结果一致。