Interferon-gamma-mediated pathways and in vitro PBMC proliferation in HIV-infected patients.
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.
Schroecksnadel
Katharina
K
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.
Winkler
Christiana
C
Werner
Ernst R
ER
Sarcletti
Mario
M
Romani
Nikolaus
N
Ebner
Susanne
S
Schennach
Harald
H
Fuchs
Dietmar
D
Zangerle
Robert
R
D000328:Adult; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D012015:Reference Standards; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D008934:Mitogens; D012333:RNA, Messenger; D007371:Interferon-gamma