Ríos Z, Ríos E O, Garcia M I, De Leon C, Guzman L M, Rodriguez W, Romero D, Hunter R
Department of Microbiology and Immunology, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico 00960-6032.
Cell Mol Biol (Noisy-le-grand). 1995;41 Suppl 1:S93-101.
This is the first time, to our knowledge, that evidence is presented showing that a polyantigenic immunomodulator (PAI), acting as a biological response modifier, can either induce or suppress HIV expression depending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-infected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and pediatric, < 2 years old) were co-cultured with PHA-stimulated PBMC from uninfected individuals in medium containing IL-2 and PAI. Parallel co-cultures were carried out in a PAI-free medium. Cultures were fed with PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p24 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-alpha) were determined on supernatants on day 14. Peripheral blood samples from each patient were evaluated at the beginning of the experiment as to total CD3, total CD19, CD3/CD4, CD3/CD8, CD16/CD56, CD8/HLA-DR and CD8/CD38 markers through flow cytometry. PAI was able to induce viral expression (up to 11,881 pg/ml of p24 antigen) in cultures showing a low (less than 16 pg/ml) or no viral titer. In contrast, in those cultures with high viral titer (10(2)-10(5) pg/ml), a substantial reduction on the titer was observed upon exposure to PAI. PAI was able to induce the production of IFN-gamma and TNF-alpha while that of IL-4 and IL-1 beta was reduced. The predominant cell type detected in the blood samples of the studied subjects were CD8+, CD8+/CD38+ or CD8+/HLA-DR+.(ABSTRACT TRUNCATED AT 250 WORDS)
据我们所知,这是首次有证据表明,一种作为生物反应调节剂的多抗原免疫调节剂(PAI),根据受感染外周血单核细胞(PBMC)的病毒载量,既能诱导也能抑制HIV表达。PAI由灭活细菌与流感病毒疫苗的混合物组成。来自HIV感染患者(无症状,年龄22 - 36岁;有症状,年龄30 - 59岁;儿科患者,小于2岁)的PBMC与来自未感染个体的经PHA刺激的PBMC在含有IL - 2和PAI的培养基中共同培养。在不含PAI的培养基中进行平行共同培养。每周用来自未感染供体的经PHA刺激的PBMC补充培养物。在第14天测定上清液中的HIV - p24抗原和细胞因子谱(IL - 1β、IL - 2、IL - 4、IFN - γ和TNF - α)。在实验开始时,通过流式细胞术对每位患者的外周血样本进行总CD3、总CD19、CD3/CD4、CD3/CD8、CD16/CD56、CD8/HLA - DR和CD8/CD38标志物评估。PAI能够在病毒滴度低(低于16 pg/ml)或无病毒滴度的培养物中诱导病毒表达(高达11,881 pg/ml的p24抗原)。相反,在那些病毒滴度高(10² - 10⁵ pg/ml)的培养物中,接触PAI后观察到滴度大幅降低。PAI能够诱导IFN - γ和TNF - α的产生,而IL - 4和IL - 1β的产生则减少。在所研究对象的血液样本中检测到的主要细胞类型为CD8⁺、CD8⁺/CD38⁺或CD8⁺/HLA - DR⁺。(摘要截断于250字)