The engagement of CD4 surface antigen in the HEL haemopoietic cell line up‐regulates the transforming growth factor‐β1 (TGF‐β1) promoter activity

In order to investigate the effect of CD4 engagement on the transforming growth factor β1 (TGF‐β1) promoter activity in haemopoietic progenitors, HEL cells were transiently transfected with a plasmid vector containing −453/+11 nucleotides of the TGF‐β1 promoter fused with the bacterial chloramphenicol acetyltransferase (CAT) gene and then treated with various agonists. Both cross‐linked CD4 mAb and envelope gp120 were able to significantly up‐regulate CAT activity with respect to the levels of activation observed in HEL cells treated with cross‐linked CD8 mAb or p24. By using deletion mutants of the TGFβ1 promoter, we found that the minimal DNA sequence still responsive to cross‐linked CD4 mAb or gp120 was located between nucleotides −453/−323 of the TGF‐β1 promoter, which contains two activating protein 1 (AP1) binding sites. In electromobility shift assays (EMSA) we could demonstrate that CD4 engagement of HEL cells induced a significant increase of AP1 binding activity at the nuclear level. Furthermore, the steady‐state mRNA of endogenous TGF‐β1 showed a small but reproducible increase when HEL cells were treated with cross‐linked CD4 mAb or gp120. Altogether, these findings suggest that the engagement of CD4 in HEL cells modulates TGF‐β1 expression, acting predominantly at the transcriptional level.