Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.1106698 on April 2, 2007

Published online before print April 2, 2007
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(Journal of Leukocyte Biology. 2007;82:72-78.)
© 2007 by Society for Leukocyte Biology

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

Guillermo Robert de Arquer*,{dagger}, Ruth Peña*, Cecilia Cabrera*, Gemma Coma*, Raul Ruiz-Hernandez*, Rosa Guerola*, Bonaventuta Clotet*, Lidia Ruiz*, José A. Esté*, M. Luz Calle{dagger} and Margarita Bofill*,{ddagger},1

* Fundació IrsiCaixa, HIVACAT, Hospital Universitari Germans Trias i Pujol, Badalona, Spain;
{dagger} Systems Biology Department, Universitat de Vic, Vic, Spain; and
{ddagger} Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

1 Correspondence: Fundació Irsicaixa, Hospital Universitari Germans Trias i Pujol, Ctra Canyet sn, 08916 Badalona, Spain. E-mail: mbofill{at}irsicaixa.es

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 ß1 (IL-12Rß1), IL-12Rß2, and IL-18R{alpha}. 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-12Rß1 and IL-18R{alpha} from HIV-1-infected patients was observed when compared with cells from HIV-1-negative donors. Higher IL-12Rß1 and IL-18R{alpha} 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-12Rß2 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-12ß2 when compared with 50% in healthy controls. Furthermore, the percentage of IL-12Rß1-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.

Key Words: IFN-{gamma} • cytokine receptors • Th1/Th2 cells • cell activation







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