The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses

The peroxisome proliferator-activated receptors (PPARs) are a family of tra nscription factors belonging to the nuclear receptor superfamily, Until rec ently, the genes regulated by PPARs were those believed to be predominantly associated with lipid metabolism. Recently, an immunomodulatory role for P PAR gamma has been described in cells critical to the innate immune system, the monocyte/macrophage. In addition, evidence for an antiinflammatory rol e of the PPAR gamma ligand, 15-deoxy-Delta(12,14)- PGJ(2) (15d-PGJ(2)) has been found. In the present studies, we demonstrate, for the first time, tha t murine helper T cell clones and freshly isolated splenocytes express PPAR gamma 1, The PPAR gamma expressed is of functional significance in that tw o ligands for PPAR gamma, 15d-PGJ(2), and a thiazolidinedione, ciglitazone, mediate significant inhibition of proliferative responses of both the T ce ll clones and the freshly isolated splenocytes, This inhibition is mediated directly at the level of the T cell and not at the level of the macrophage /APC. Finally, we demonstrate that the two ligands for PPAR gamma mediate i nhibition of IL-2 secretion by the T cell clones while not inhibiting IL-2- induced proliferation of such clones. The demonstration of the expression a nd function of PPAR gamma in T cells reveals a new level of immunoregulator y control for PPARs and significantly increases the role and importance of PPAR gamma in immunoregulation.