Skewed expression and up-regulation of the IL-12 and IL-18 receptors in resting and activated CD4 T cells from HIV-1-infected patients

Abstract

IL-12 and IL-18 synergistically induce the production of IFN- by resting and activated T cells. To evaluate whether this induction was affected in HIV-1-infected patients, PBMC or isolated CD4 T cells were cultured with IL-12 plus IL-18, anti-CD3 plus anti-CD28, or PHA for 72 h. Cell samples were labeled daily to assess the levels of IL-12 receptor 1 (IL-12R 1), IL-12R 2, and IL-18R . Culture supernatants were analyzed for the presence of Th1- and Th2-related cytokines by ELISA or cytometric bead array and analyzed by flow cytometry. A twofold increase in the percentage of CD4-resting T cells expressing IL-12R 1 and IL-18R from HIV-1-infected patients was observed when compared with cells from HIV-1-negative donors. Higher IL-12R 1 and IL-18R expression correlated (r 0.87; P<0.007) to increased production of IFN- by isolated CD4 T cells in the presence of IL-12 and IL-18. Moreover, exogenous IL-12 and IL-18 induced the upregulation of IL-12R 2 to twice higher in CD4 T cells from HIV-1-positive individuals compared with controls. Conversely, upon activation with anti-CD3 and anti-CD28 antibodies, only 25% of the CD4 T cells from HIV-1 patients showed an increase in the IL-12 2 when compared with 50% in healthy controls. Furthermore, the percentage of IL-12R 1-positive cells correlated inversely with the CD4 nadir of patients, suggesting that deregulation of the IL-12 and IL-18 pathways may play a role in the immunopathogenesis of HIV-1 infection. J. Leukoc. Biol. 82: 72–78; 2007.