Transcriptional regulation of the CD127 gene in primary human CD8 T-cells

Abstract

Factors regulating expression of the IL-7 receptor throughout the CD8 T-cell life-span have not been fully characterized but IL-7 has been shown to down regulate the IL-7 receptor alpha-chain (CD127) at the cell surface. Here we show that IL-7 induced a decline in the level of total CD127 transcripts in CD8 T-cells. Also, IL-7 had no effect on CD127 mRNA stability, or alternative splicing. We also find that down regulation of CD127 by IL-7 requires de novo transcript and protein synthesis. Reporter assay analysis of the CD127 promoter showed that sequences up to 3kb upstream of the TATA box are required for basal CD127 gene expression. Within this region a Glucocorticoid Response Element near -2.2kb was identified as an important regulator of CD127 transcription. Conversely, IL-7 did not down regulate the ∼3kb promoter construct suggesting that the IL-7 responsive elements may lie outside this region.