Regulation of lymphokine gene expression.

Abstract

T cell activation induces the expression of multiple lymphokine genes. Different lymphokine genes can be induced by distinct pathways and may be coordinately or differentially expressed depending on the stimulus. The regulation of lymphokine gene expression occurs at multiple levels. Since quiescent T cells do not transcribe lymphokine genes, the primary regulation of lymphokine expression occurs at the transcriptional level. However, lymphokine gene expression is also regulated post-transcriptionally. AUUUA multimers present in the 3$\sp\prime$ untranslated region of mature lymphokine transcripts have been implicated as cis-acting regulatory sequences that control mRNA stability and translational efficiency. Two structurally related factors, termed AU-B and AU-C, are present in T cell cytoplasmic extracts and bind selectively to AUUUA multimers. AU-B and AU-C RNA-binding activities are not present in quiescent T cells but are induced by T cell receptor-mediated stimulation and display kinetics that parallel the expression of several lymphokine genes. Based upon their pattern of expression and precise binding specifity, AU-B and AU-C could be cytoplasmic regulators of lymphokine mRNA metabolism.