The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis

Peroxisome proliferator-activated receptor (PPAR)-gamma is a nuclear hormon e receptor that serves as a trans factor to regulate lipid metabolism. Inte nse interest is focused on PPAR-gamma and its ligands owing to its putative role in adipocyte differentiation. Little is known, however, about the fun ctions of PPAR-gamma in the immune system, especially in T lymphocytes. We demonstrate that both naive and activated ovalbumin-specific T cells from D O11.10-transgenic mice express PPAR-gamma, mRNA and protein. In order to de termine the function of PPAR-gamma, T cells were stimulated with phorbol 12 -myristate 13-acetate and ionomycin or antigen and antigen-presenting cells . Simultaneous exposure to PPAR-gamma ligands (e, g. 15-deoxy-Delta (12, 14 )- prostaglandin J(2), troglitazone) showed drastic inhibition of prolifera tion and significant decreases in cell viability. The decrease in cell viab ility was due to apoptosis of the T lymphocytes, and occurred only when cel ls were treated with PPAR-gamma, and not PPAR-alpha agonists, revealing spe cificity of this response for PPAR-gamma. These observations suggest that P PAR-gamma agonists play an important role in regulating T cell-mediated imm une responses by inducing apoptosis. T cell death via PPAR-gamma ligation m ay act as a potent anti-inflammatory signal in the immune system, and ligan ds could possibly be used to control disorders in which excessive inflammat ion occurs.