Activation-induced PPARgamma expression sensitizes primary human T cells toward apoptosis

Phytohemagglutinin (PHA) elicited expression of peroxisome proliferator-activated receptor γ (PPARγ) in primary human T cells via the PPARγ3 promoter, as shown by reverse transcription-polymerase chain reaction. Electrophoretic mobility shift assay demonstrated no correlation between PPARγ expression and its activation. However, addition of specific PPARγ agonists such as ciglitazone or 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) for 1 h following PHA pretreatment provoked PPARγ activation verified by supershift analysis. Taking the proapoptotic properties of PPARγ into consideration, we analyzed induction of apoptosis in activated T cells in response to PPARγ agonists. Cells exposed to PPARγ agonists alone revealed minor cell death compared with controls, whereas treatment with 15d-PGJ2 or ciglitazone for 4 h subsequent to PHA stimulation significantly increased cell demise, which was attenuated by the pan-caspase inhibitor zVAD, pointing to apoptosis as the underlying mechanism. These data may be relevant for pathophysiological conditions accompanied with lymphopenia of T cells under conditions such as sepsis.