Effects of cytokines on HIV-1 production by thymocytes

The thymus is essential for normal T cell development and is particularly active during fetal and postnatal life. Here we describe in vitro studies of HIV-infected thymocytes cultured with cytokines normally produced in the thymus. Virus expression was determined by measuring p24 antigen levels in the culture supernatants. Addition of IL-2+IL-4 and IL-4+IL-7 to the HIV-infected cultures of both fetal and postnatal thymocytes resulted in various levels of synergistic expression of p24 antigen. When differences in phenotype between HIV-infected and non-infected (sham-treated) cultures from the same specimen were evaluated, there was a decrease in the percentages and absolute numbers of CD4-bearing cells in HIV-infected thymocytes cultured with IL-2+IL-4. Studies were done to determine if synergy in HIV expression was mediated by activation, proliferation or induction or suppression of other cytokines. We found a higher percentage of activated CD4+CD8+/high cells in thymocytes cultured with IL-2+IL-4 and IL-4+IL-7 than in thymocytes cultured with IL-2+IL-7. Proliferation was higher in thymocytes cultured with cytokine combinations but did not correlate with those conditions showing synergy. IL-4 reduced IFN-gamma production by thymocytes cultured with IL-2 in both HIV-infected and non-infected thymocytes. In addition, exogenous IFN-gamma decreased p24 expression by HIV-infected thymocytes when cultured with IL-4 alone, with IL-2+IL-4 or IL-4+IL-7. These results suggest that suppression of IFN-gamma by IL-4 may combine with cell activation and proliferation to produce synergy of virus expression observed with IL-2+IL-4 and IL-4+IL-7.