title: 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-gamma 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 beta1 (IL-12Rbeta1), IL-12Rbeta2, and IL-18Ralpha. 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-12Rbeta1 and IL-18Ralpha from HIV-1-infected patients was observed when compared with cells from HIV-1-negative donors. Higher IL-12Rbeta1 and IL-18Ralpha expression correlated (r=0.87; P<0.007) to increased production of IFN-gamma by isolated CD4 T cells in the presence of IL-12 and IL-18. Moreover, exogenous IL-12 and IL-18 induced the up-regulation of IL-12Rbeta2 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-12beta2 when compared with 50% in healthy controls. Furthermore, the percentage of IL-12Rbeta1-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.
authors.affiliation: Fundació IrsiCaixa, HIVACAT, Hospital Universitari Germans Trias i Pujol, Ctra Canyet sn, 08916 Badalona, Spain.
authors.forename: Guillermo Robert
authors.initials: GR
authors.lastname: de Arquer
authors.forename: Ruth
authors.initials: R
authors.lastname: Peña
authors.forename: Cecilia
authors.initials: C
authors.lastname: Cabrera
authors.forename: Gemma
authors.initials: G
authors.lastname: Coma
authors.forename: Raul
authors.initials: R
authors.lastname: Ruiz-Hernandez
authors.forename: Rosa
authors.initials: R
authors.lastname: Guerola
authors.forename: Bonaventuta
authors.initials: B
authors.lastname: Clotet
authors.forename: Lidia
authors.initials: L
authors.lastname: Ruiz
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
authors.forename: M Luz
authors.initials: ML
authors.lastname: Calle
authors.forename: Margarita
authors.initials: M
authors.lastname: Bofill
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000209:etiology / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D053724:Receptors, Interleukin-18 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18