Abstracts (complete list) - Wissenschaft Online

Karsten Gülow, Marcin Kaminski, Peter H. Krammer
HIV-Tat induced generation of Reactive Oxygen Species
sensitizes T cells towards Activation-Induced Cell Death
The elimination of activated T cells during the termination phase of an immune response
is called Activation Induced Cell Death (AICD). AICD is induced via stimulation of the
death receptor CD95 (APO-1, Fas) by its ligand CD95L. In AIDS patients, AICD is
strongly enhanced. Here, we show that Reactive Oxygen Species (ROS) generated upon
T cell activation function as crucial second messengers in activation-induced CD95L
expression. The oxidative signal combined with simultaneous increase in intracellular
Ca2+ constitutes for minimal requirement to induce CD95L expression. Either signal
alone is insufficient. Further, we show that HIV-Tat induces ROS generation and
depletion of reduced glutathione (GSH). The increase in ROS induced by HIV-Tat
enhances T cell receptor (TCR) signalling. Thus, cells preincubated with Tat and
stimulated via the TCR reveal a strong increase in the ROS signal leading to a significant
increase in CD95L expression and AICD. Since CD4 stimulation can induce Ca2+ influx
into the cytosol, ROS generation due to Tat treatment is sufficient to induce AICD.
Therefore, our data provide a possible explanation for CD4+ T lymphocyte depletion
during progression of AIDS.