1. Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients.
- Author
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Schroecksnadel, Katharina, Winkler, Christiana, Werner, Ernst R., Sarcletti, Mario, Romani, Nikolaus, Ebner, Susanne, Schennach, Harald, Fuchs, Dietmar, and Zangerle, Robert
- Subjects
HIV infections ,IMMUNODEFICIENCY ,IMMUNOLOGICAL deficiency syndromes ,CELLULAR immunity ,ANTIGENS ,MITOGENS - Abstract
HIV infection is characterized by progressive immunodeficiency: HIV-infected peripheral blood mononuclear cells (PBMCs) cannot properly react to stimulation with allo-antigens and mitogens. In this study, we examined interferon-γ (IFN-γ)-mediated pathways and the proliferative response of mitogen-stimulated HIV-infected PBMCs in vitro. PBMCs of 30 HIV-infected patients were stimulated with the mitogens concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM). Mitogen stimulation induced expression of IFN-γ, GTP cyclohydrolase I (GCH-I), and indoleamine (2,3)-dioxygenase (IDO) resulting in enhanced neopterin formation and tryptophan degradation by HIV-infected and control PBMCs. IFN-γ concentrations correlated with neopterin levels and tryptophan degradation. Proliferative responses to PHA and PWM cytokine were lower in HIV patients, with IFN-γ formation predicting proliferative responses. Higher mRNA expression of IFN-γ, GCH-I and IDO after 6 h was related to better proliferative responses in HIV-infected PBMCs. In conclusion, induction of IFN-γ and subsequent enzymes appears to importantly influence the proliferative response of HIV-infected PBMCs in vitro, suggesting a prominent role of the cytokine in the development of immunodeficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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