CHANGES IN VIRAL EXPRESSION AND CYTOKINE PROFILE INDUCED BY A POLYANTIGENIC IMMUNOMODULATOR IN HIV-INFECTED PERIPHERAL-BLOOD MONONUCLEAR-CELLS

This is the first time, to our knowledge, that evidence is presented s howing that a polyantigenic immunomodulator (PAI), acting as a biologi cal response modifier, can either induce or suppress HIV expression de pending on the viral load of infected PBMC. PAI consists of a mixture of inactivated bacteria with influenza virus vaccine. PBMC from HIV-in fected patients (asymptomatic, age 22-36, symptomatic, age 30-59 and p ediatric, <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 wit h PHA-stimulated PBMC from uninfected donors on a weekly basis. HIV-p2 4 ag and cytokine profiles (IL-1 beta, IL-2, IL-4, IFN-gamma and TNF-a lpha) were determined on supernatants on day 14. Peripheral blood samp les from each patient were evaluated at the beginning of the experimen t 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 v iral expression (up to 11,881 pg/ml of p24 antigen) in cultures showin g 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 reduc tion on the titer was observed upon exposure to PAI. PAI was able to i nduce 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 bloo d 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 lym phocyte subset in the original blood samples. Other mechanisms, possib ly related to cytotoxic CD8(+) cells, might account for PAI suppressiv e effect on viral expression observed in those PBMC cultures with high titer.