Glucocorticoid hormone-induced modulation of gene expression and regulation of T-cell death: role of GITR and GILZ, two dexamethasone-induced genes

Regulation of T-cell survival is a physiological process involved in determ ining the immune response development, and also the expansion of T-cell tum ours, Glucocorticoid hormones (GCH) have been implicated as regulators of T -lymphocyte growth and differentiation. In particular, GCH which by themsel ves are apoptosis activators and induce T-cell death, can also counteract a poptosis activated by other stimuli, for example antigen-TCR interaction, A number of biochemical events constitute different GCH-activated death-trig gering pathways and transcription activity regulation, either upstream and/ or downstream in the pathways, is essential to apoptosis, Similarly, GCH-me diated inhibition of apoptosis also requires gene transcription regulation, In particular, between a number of GCH-induced genes, GITR and GILZ can in hibit apoptosis through interaction with mechanisms involved in T-cell surv ival regulation including the NF-kappa B transcription activity and the exp ression of the Fas/Fast system. These observations indicate that this GCH-a ctivated dual effect, induction and/or inhibition of T-cell death, requires transcription regulation.