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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Interferon-γ-mediated pathways and in vitro PBMC proliferation in HIV-infected patients

Katharina Schroecksnadel1 / Christiana Winkler2 / Ernst R. Werner3 / Mario Sarcletti4 / Nikolaus Romani5 / Susanne Ebner6 / Harald Schennach7 / Dietmar Fuchs8 / Robert Zangerle9

1Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, A-6020 Innsbruck, Austria and Department of General Internal Medicine, University Clinic of Innsbruck, Medical University of Innsbruck, A-6020 Innsbruck, Austria

2Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, A-6020 Innsbruck, Austria

3Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, A-6020 Innsbruck, Austria

4Department of Dermatology and Venereology, University Clinic of Innsbruck, Medical University of Innsbruck, A-6020 Innsbruck, Austria

5Department of Dermatology and Venereology, University Clinic of Innsbruck, Medical University of Innsbruck, A-6020 Innsbruck, Austria

6Department of Dermatology and Venereology, University Clinic of Innsbruck, Medical University of Innsbruck, A-6020 Innsbruck, Austria

7Central Institute of Blood Transfusion and Immunology, University Hospital, A-6020 Innsbruck, Austria

8Division of Biological Chemistry, Biocenter, Medical University of Innsbruck, A-6020 Innsbruck, Austria

9Department of Dermatology and Venereology, University Clinic of Innsbruck, Medical University of Innsbruck, A-6020 Innsbruck, Austria

Corresponding author

Citation Information: Biological Chemistry. Volume 390, Issue 2, Pages 115–123, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2009.018, November 2008

Publication History:
Received:
2008-05-27
Accepted:
2008-10-27
Published Online:
2008-11-29

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.

Keywords: HIV; IDO; neopterin; peripheral blood mononuclear cells (PBMCs); proliferation; tryptophan degradation

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