Changes in viral expression and cytokine profile induced by a polyantigenic immunomodulator in HIV-infected peripheral blood mononuclear cells
Ríos, Z.; Ríos, E.O.; Garcia, M.I.; De Leon, C.; Guzman, L.M.; Rodriguez, W.; Romero, D.; Hunter, R.
Cellular and Molecular Biology 41(Suppl): S93-S101
1995
ISSN/ISBN: 0145-5680 PMID: 8574153 Document Number: 442158
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, lt 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+. However, viral expression was induced by PAI in cultures with minimal or zero level of p24 ag regardless of the predominant lymphocyte subset in the original blood samples. Other mechanisms, possibly related to cytotoxic CD8+ cells, might account for PAI suppressive effect on viral expression observed in those PBMC cultures with high titer.