Differential Expression of Fas Ligand in Th1 and Th2 Cells Is Regulated by Early Growth Response Gene and NF-AT Family Members

• Published in: The Journal of immunology (1950) Vol. 166; no. 7; pp. 4534 - 4542
• Main Authors: Dzialo-Hatton, Robin, Milbrandt, Jeffrey, Hockett, Richard D., Jr, Weaver, Casey T
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2001
• Subjects: Animals; Base Sequence; Cell Line; Cell Nucleus - immunology; Cell Nucleus - metabolism; Cyclosporine - pharmacology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Early Growth Response Protein 1; Early Growth Response Protein 3; Egr1 protein; Egr2 protein; Egr3 protein; Fas Ligand Protein; fas Receptor - metabolism; FasL protein; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Humans; Hybridomas; Immediate-Early Proteins; Ligands; Lymphocyte Activation - genetics; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; Multigene Family - immunology; NF-AT protein; NFATC Transcription Factors; Nuclear Proteins; Promoter Regions, Genetic - drug effects; Promoter Regions, Genetic - genetics; Promoter Regions, Genetic - immunology; RNA, Messenger - biosynthesis; Sequence Deletion; Sp1 Transcription Factor - genetics; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - physiology; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.7.4534

Inducible expression of Fas ligand (CD95 ligand) by activated T cells and the resulting apoptosis of CD95-bearing cells is a critical component of peripheral T cell homeostasis and cytotoxic effector mechanisms. Transcriptional control of the expression of Fas ligand has been attributed to a number of factors, including early growth response gene 2 (Egr2), Egr3, Sp1, and NF-AT, although a direct contribution of NF-AT is controversial. The present study confirms a role for Egr factors and indicates that NF-AT is essential for optimal expression of murine Fas ligand through a direct interaction with an NF-AT consensus element. The role of these factors was further defined by studying the differential expression of Fas ligand in Th1 and Th2 lines derived from DO11.10 TCR transgenic mice. EMSA analyses of a composite Egr/NF-AT site showed recruitment of Sp1 to this site in Th2 cells, but not in Th1 cells. Furthermore, gel-shift analyses demonstrated the binding of Egr1, 2, and 3 in Th2 cells and Egr1 and 2, but not Egr3 in Th1 cells at a known Egr site. Northern analysis corroborated the lack of Egr3 in Th1 cells. Differential usage of these transcription factors by Th1 and Th2 cells suggests a potential mechanism underlying the differential expression of Fas ligand by distinct T cell lineages.