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Sven Baumann

Publications and source records attributed to Sven Baumann.

21 records · Page 2Linked to original sources

Viral IFN-regulatory factors inhibit activation-induced cell death via two positive regulatory IFN-regulatory factor 1-dependent domains in the CD95 ligand promoter.

The CD95 (also called APO-1/Fas) system plays a major role in the induction of apoptosis in lymphoid and nonlymphoid tissues. The CD95 ligand (CD95L) is induced in response to a variety of signals, including IFN-gamma and TCR/CD3 stimulation. Here we report the identification of two positive regulatory IFN-regulatory factor-dependent domains (PRIDDs) in the CD95L promoter and its 5' untranslated region, respectively. EMSAs demonstrate specific binding of IFN-gamma-induced IFN-regulatory factor 1 (IRF-1) to the PRIDD sequences. Ectopic IRF-1 expression induces CD95L promoter activity. Furthermore, we demonstrate that PRIDDs play an important role in TCR/CD3-mediated CD95L induction. Most interestingly, viral IRFs of human herpes virus 8 (HHV8) totally abolish IRF-1-mediated and strongly reduce TCR/CD3-mediated CD95L induction. We demonstrate here for the first time that viral IRFs inhibit activation-induced cell death. Thus, these results demonstrate an important mechanism of HHV8 to modulate the immune response by down-regulation of CD95L expression. Inhibition of CD95-dependent T cell function might contribute to the immune escape of HHV8.

Apoptosis↗

Vitamin E inhibits CD95 ligand expression and protects T cells from activation-induced cell death.

Apoptosis is a morphologically distinct form of cell death involved in many physiological and pathological processes. Expression of the CD95 (APO-1/Fas) ligand (CD95L) is critically involved in activation-induced cell death (AICD) of activated T cells. Here we show that the natural free radical scavenger vitamin E suppresses the activity of the transcription factors NF-kappa B and AP-1, thus blocking expression of CD95L and preventing T cell AICD. Since AICD is a major cause of T cell depletion in AIDS, we examined 35 HIV-1-positive individuals and found that their T cells are more susceptible to AICD than are T cells isolated from healthy controls. Administration of vitamin E suppresses CD95L mRNA expression and protects T cells of HIV-1-infected individuals from CD95-mediated apoptosis. This evidence that vitamin E can affect T cell survival may merit further clinical investigation.

Adult↗

Regulation of T cell apoptosis during the immune response.

Apoptosis of T-lymphocytes is a fundamental process regulating antigen receptor repertoire selection during T cell maturation and homeostasis of the immune system. It also plays a key role in elimination of autoreactive lymphocytes. Resting mature T cells are activated by antigen to elicit an appropriate immune response. In contrast, preactivated T cells undergo activation-induced cell death (AICD) in response to TCR triggering alone. Thus, death by apoptosis is essential for function, growth and differentiation of T-lymphocytes. This review focuses on apoptosis mechanisms involved in T cell development and during the course of an immune response.

Animals↗