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HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death

Termination of an immune response requires elimination of activated T lymphocytes by activation-induced cell death (AICD). In AICD, CD95 (Apo-1/Fas) ligand (L) triggers apoptosis of CD95-positive activated T lymphocytes. In AIDS patients, AICD is strongly enhanced and accelerated. We and others have...

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Bibliographic Details
Main Authors: Gülow, Karsten (Author) , Li-Weber, Min (Author) , Krammer, Peter H. (Author)
Format: Article (Journal)
Language:English
Published: 1 May 2005
In: The journal of immunology
Year: 2005, Volume: 174, Issue: 9, Pages: 5249-5260
ISSN:1550-6606
DOI:10.4049/jimmunol.174.9.5249
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.174.9.5249
Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/174/9/5249
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Author Notes:Karsten Gülow, Marcin Kamiński, Katalin Darvas, Dorothee Süss, Min Li-Weber, and Peter H. Krammer
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Summary:Termination of an immune response requires elimination of activated T lymphocytes by activation-induced cell death (AICD). In AICD, CD95 (Apo-1/Fas) ligand (L) triggers apoptosis of CD95-positive activated T lymphocytes. In AIDS patients, AICD is strongly enhanced and accelerated. We and others have previously shown that HIV-1 trans-activator of transcription (HIV-1 Tat) sensitizes T cells toward CD95-mediated apoptosis and up-regulates CD95L expression by affecting the cellular redox balance. In this study, we show that it is hydrogen peroxide (H2O2) that functions as an essential second messenger in TCR signaling. The H2O2 signal combined with simultaneous calcium (Ca2+) influx into the cytosol constitutes the minimal requirement for induction of CD95L expression. Either signal alone is insufficient. We further show that HIV-1 Tat interferes with TCR signaling and induces a H2O2 signal. H2O2 generated by HIV-1 Tat combines with CD4-dependent calcium influx and causes massive T cell apoptosis. Thus, our data provide an explanation for CD4+ T lymphocyte depletion during progression of AIDS.
Item Description:Published online April 20, 2005
Gesehen am 04.03.2021
Physical Description:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.174.9.5249

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