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 determining the immune response development, and also the expansion of T-cell tumours. Glucocorticoid hormones (GCH) have been implicated as regulators of T-lymphocyte growth and differentiation. In particular, GCH which by themselves are apoptosis activators and induce T-cell death, can also counteract apoptosis activated by other stimuli, for example antigen-TCR interaction. A number of biochemical events constitute different GCH-activated death-triggering pathways and transcription activity regulation, either upstream and/or downstream in the pathways, is essential to apoptosis. Similarly, GCH-mediated inhibition of apoptosis also requires gene transcription regulation. In particular, between a number of GCH-induced genes, GITR and GILZ can inhibit apoptosis through interaction with mechanisms involved in T-cell survival regulation including the NF-kappaB transcription activity and the expression of the Fas/FasL system. These observations indicate that this GCH-activated dual effect, induction and/or inhibition of T-cell death, requires transcription regulation.