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Cutting edge: distal regulatory elements are required to achieve selective expression of IFN-gamma in Th1/Tc1 effector cells.

Soutto M, Zhou W, Aune TM
J Immunol. 2002 169 (12): 6664-7

PMID: 12471094 · DOI:10.4049/jimmunol.169.12.6664

Using a transgenic approach, we analyzed the contribution of introns located within the IFN-gamma gene and distal regulatory regions to IFN-gamma gene expression. Intron 1 and 3 from the IFN-gamma 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-gamma gene, but rather for cell lineage-specific expression. An 8.6-kb human IFN-gamma transgene was sufficient to yield high level expression but a 191-kb IFN-gamma transgene with approximately 90 kb of flanking 5' and 3' sequence was necessary to achieve both high level and Th1 selective expression of human IFN-gamma.

MeSH Terms (16)

Animals Cells, Cultured Dose-Response Relationship, Immunologic Enhancer Elements, Genetic Humans Interferon-gamma Introns Jurkat Cells Mice Mice, Inbred C57BL Mice, Transgenic Promoter Regions, Genetic Regulatory Sequences, Nucleic Acid T-Lymphocytes, Cytotoxic Th1 Cells Transfection

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