Glucocorticoids are small lipophilic compounds that mediate their many biol
ogical effects by binding an intracellular receptor (GR) that, in turn, tra
nslocates to the nucleus and directly or indirectly regulates gene transcri
ption. Perhaps the most recognized biologic effect of glucocorticoids on pe
ripheral T cells is immunosuppression, which is due to inhibition of expres
sion of a wide variety of activation-induced gene products. Glucocorticoids
have also been implicated in Th lineage development (favoring the generati
on of Th2 cells) and, by virtue of their downregulation of fasL expression,
the inhibition of activation-induced T cell apoptosis. Glucocorticoids are
also potent inducers of apoptosis, and even glucocorticoid concentrations
achieved during a stress response can cause the death of CD4(+)CD8(+) thymo
cytes. Perhaps surprisingly, thymic epithelial cells produce glucocorticoid
s, and based upon in vitro and in vivo studies of T cell development it has
been proposed that these locally produced glucocorticoids participate in a
ntigen-specific thymocyte development by inhibiting activation-induced gene
transcription and thus increasing the TCR signaling thresholds required to
promote positive acid negative selection. It is anticipated that studies i
n animals with tissue-specific GR-deficiency will further elucide how gluco
corticoids affect T cell development and function.