Cutting Edge: Distal Regulatory Elements Are Required to Achieve Selective Expression of IFN-γ in Th1/Tc1 Effector Cells

Abstract

Using a transgenic approach, we analyzed the contribution of introns located within the IFN-γ gene and distal regulatory regions to IFN-γ gene expression. Intron 1 and 3 from the IFN-γ gene displayed strong enhancer activity. This activity appeared to be dependent upon integration into the genome but resulted in a loss of Th1 selectivity. We also found that distal regulatory elements are not required for high level expression of the human IFN-γ gene, but rather for cell lineage-specific expression. An 8.6-kb human IFN-γ transgene was sufficient to yield high level expression but a 191-kb IFN-γ transgene with ∼90 kb of flanking 5′ and 3′ sequence was necessary to achieve both high level and Th1 selective expression of human IFN-γ.