To acquire the effector phenotype, CD8⁺ T cells must overcome a regulatory threshold that maintains the naïve status. This requires suppressing or overcoming the effect of genes that maintain the threshold, however this program is not fully understood. Based on findings in B cells and CD4 T cells, a likely determinant of this regulatory threshold in lymphocytes is the glucocorticoid induced leucine zipper (GILZ).  GILZ is strongly induced by glucocorticoids (steroids), the standard therapy for autoimmune diseases such as systemic lupus erythematosus (SLE). GILZ expression is protective against autoimmune diseases driven by CD4 Th17 cells and B cells such as SLE, in which normal GILZ expression is partially lost and CD8 T cell activity is associated with pathogenesis. In vitro, GILZ is rapidly downregulated upon CD8 T cell activation and proliferative burst. Furthermore, we have identified a putative regulatory region in the GILZ locus unique to T cells that appears to be bound by the key CD8 T cell transcription factors Tcf-1 and T-bet. We propose that Tcf-1 positively regulates GILZ transcription and contributes to maintaining the naïve status, whereas T-bet suppresses GILZ expression to overcome the threshold and drive acquisition of the effector phenotype. Collectively, these data suggest a key transcriptional network that contributes to the regulation of CD8 T cell activation that may be therapeutically targeted to promote cellular immunity, or to suppress inflammation in the context of autoimmune disease.