Schroecksnadel Katharina, Winkler Christiana, Werner Ernst R, Sarcletti Mario, Romani Nikolaus, Ebner Susanne, Schennach Harald, Fuchs Dietmar, Zangerle Robert
Department of General Internal Medicine, University Clinic of Innsbruck, Medical University of Innsbruck, and Central Institute of Blood Transfusion and Immunology, University Hospital, A-6020 Innsbruck, Austria.
Biol Chem. 2009 Feb;390(2):115-23. doi: 10.1515/BC.2009.018.
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-gamma (IFN-gamma)-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-gamma, 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-gamma concentrations correlated with neopterin levels and tryptophan degradation. Proliferative responses to PHA and PWM cytokine were lower in HIV patients, with IFN-gamma formation predicting proliferative responses. Higher mRNA expression of IFN-gamma, GCH-I and IDO after 6 h was related to better proliferative responses in HIV-infected PBMCs. In conclusion, induction of IFN-gamma 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.
