Peroxisome proliferator–activated receptor gamma (PPAR-γ) is a nuclear hormone receptor found mainly in adipocytes, but has also recently been found in fibroblasts, myocytes, macrophages, and epithelial cells. 1 In mice, there are two isoforms of PPAR-γ—PPAR-γ1 and PPAR-γ2. While PPAR-γ1 is found at low levels in many cell types, the PPAR-γ2 isoform seems restricted to adipocytes. The functional significance of the two isoforms has not yet been determined. 2 Synthetic ligands for PPAR-γ include the antidiabetic drug, troglitazone, as well as other thiazolidinediones and LY, 171883. Natural ligands include linoleic acid and 15-deoxy∆ 12, 14PGJ2 (a metabolite of prostaglandin D2). 3, 4 Upon ligand binding, PPARs heterodimerize with the retinoic X receptor. This complex regulates gene expression by acting as a transcription factor, binding to PPAR-responsive elements (PPREs) in promoter regions. Binding of the receptors by ligand can induce a variety of responses including fat cell differentiation, regulation of colonic epithelial cell differentiation, and TNF-α stimulation in macrophages. 5–7 To date, there is very little information concerning the effects of PPAR-γ activation on the immune system. This topic is extremely important and timely due to the recent use of synthetic PPAR-γ agonists (ie, the thiazolidinediones) in the treatment of non-insulin-dependent diabetes. Therefore, we have studied the expression and function of this receptor in T lymphocyte development. Interestingly, naive mouse T cells isolated from DO11. 10 T cell receptor transgenic mice express mRNA for the PPAR-γ1 isoform, as well as PPAR-γ protein (FIG. 1). Also, when naive mouse T cells are cultured with PPAR-γ (but not PPAR-α) agonists in the presence of either antigen and antigen-presenting cells or PMA and ionomycin, the proliferation of the cells is inhibited in a dose-dependent fashion. The inhibition of proliferation is statistically significant (p< 0.05) at concentrations greater than 3 µM (FIG. 2). To determine if the observed decrease in proliferation was due to a decrease in cell viability, MTT assays were performed. FIGURE 2 shows that PPAR-γ agonists do, in fact, induce cell death in mouse T lymphocytes. Significant inhibition of viability was observed at concentrations ranging from 3 to 100 µM. The PPAR-α agonist WY, 14643 did not induce cell death, suggesting that the response is specific for PPAR-γ. aAddress for correspondence: Richard P. Phipps, Cancer Center Box 704, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642. Voice: 716/275-8326; fax: 716/461-4019. Richard_Phipps@ urmc. rochester. edu