Nuclear factor of activated T cells (NFAT) is a possible target for dexamethasone in thymocyte apoptosis

Cell death plays a critical role in the generation of an effective immune system. During maturation T lymphocytes are generated, censored and eliminated in the thymus. These events an temporally associated with developmental changes in the levels of transcription factors including NFAT. The NFAT transcription factor (nuclear factor of activated T cells) is implicated in the regulation of T-lymphocyte proliferation and transcriptional activation of genes encoding lymphokines. It has been demonstrated that discontinuities in the inducibility of NFAT and AP-1 transcription factors occur during transition of immature thymocytes into cortical thymocytes which are eliminated by apoptosis. To understand the molecular basis of these developmental intrathymic changes, we studied DNA-binding activities of transcription factors during dexamethasone-induced apoptosis of immature thymocytes. We observed a specific loss of NFAT DNA-binding activity after dexamethasone treatment: It correlated with a selective disappearance of one out of two AP-1 complexes. Our data suggest that NFAT complex is a possible target in dexamethasone-induced apoptosis. (C) 1997 Academic Press Limited.