Nair M P, Schwartz S A
State University of New York at Buffalo, USA.
Brain Behav Immun. 1995 Mar;9(1):20-30. doi: 10.1006/brbi.1995.1003.
In order to examine the potential role of stress hormones and circulating HIV-1-derived products in the progression of HIV infections, we developed an in vitro model system that investigates the effects of cortisol and HIV soluble gene products on the natural killer cell activity of normal lymphocytes. The system employs a 4-h 51Cr release assay and K562- and LAV-infected 8E5/LAV target cells. Direct addition of cortisol at 0.05, 0.1, and 0.2 microgram/ml or the HIV recombinant peptide, env-gag, at 1, 10, and 50 ng/ml separately to the mixture of effector and prelabeled target cells did not produce any significant immunoregulatory effects on NK cell activity against either target. However, cortisol or env-gag at concentrations that did not produce any inhibitory effect on NK activity when used separately, manifested significant inhibitory effects when added in combination. Suppression was evident at concentrations as low as 1 ng/ml of env-gag and 0.05 microgram/ml of cortisol and was observed at different effector:target cell ratios. Suppression was not caused by nonspecific toxicity of cortisol or HIV peptides when added in combination to the effector cells nor was due to decreased susceptibility of targets to lysis by effector cells. A non-HIV viral antigen (Rubeola virus) and another HIV-1 envelope-derived sequence (env 578-608 aa) were used as controls separately or in combination with cortisol and did not produce significant inhibition thus demonstrating the specificity of env-gag-induced inhibition. The synergistic inhibitory effect of cortisol- and HIV-derived soluble products in patients with HIV infections are consistent with a model that proposes that stress and circulating HIV-1-derived products may be involved in the progression of HIV infections.
为了研究应激激素和循环中的HIV - 1衍生产物在HIV感染进展中的潜在作用，我们开发了一种体外模型系统，用于研究皮质醇和HIV可溶性基因产物对正常淋巴细胞自然杀伤细胞活性的影响。该系统采用4小时的51Cr释放试验以及K562和LAV感染的8E5/LAV靶细胞。分别向效应细胞和预先标记的靶细胞混合物中直接添加0.05、0.1和0.2微克/毫升的皮质醇或1、10和50纳克/毫升的HIV重组肽env - gag，对针对任一靶细胞的NK细胞活性均未产生任何显著的免疫调节作用。然而，单独使用时对NK活性无任何抑制作用的皮质醇或env - gag浓度，在联合添加时表现出显著的抑制作用。在低至1纳克/毫升的env - gag和0.05微克/毫升的皮质醇浓度下抑制作用就很明显，并且在不同的效应细胞：靶细胞比例下均能观察到。联合添加到效应细胞中的皮质醇或HIV肽的非特异性毒性并非抑制作用的原因，也不是由于靶细胞对效应细胞裂解的敏感性降低所致。一种非HIV病毒抗原（风疹病毒）和另一种HIV - 1包膜衍生序列（env 578 - 608氨基酸）分别单独使用或与皮质醇联合使用时均未产生显著抑制作用，从而证明了env - gag诱导抑制的特异性。皮质醇和HIV衍生的可溶性产物在HIV感染患者中的协同抑制作用与一种模型一致，该模型提出应激和循环中的HIV - 1衍生产物可能参与HIV感染的进展。
