Glucocorticoids in T cell development and function

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.