Abstract
We have identified RORgamma t, a novel, thymus-specific isoform of the orphan nuclear receptor RORgamma that is expressed predominantly in CD4+ CD8+ double-positive thymocytes. Ectopic expression of RORgamma t protects T cell hybridomas from activation-induced cell death by inhibiting the upregulation of Fas ligand. Following hybridoma stimulation, RORgamma t also inhibits IL-2 production but does not affect the induction of Nur-77 and Egr-3 nor the upregulation of CD69. Both the ligand-binding and DNA-binding domains of RORgamma t are required for this effect. We propose that the role of RORgamma t expression in immature thymocytes is to inhibit Fas ligand expression and cytokine secretion following engagement of their TCR during positive or negative selection.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Base Sequence
-
Cloning, Molecular
-
DNA, Complementary
-
Fas Ligand Protein
-
Female
-
Gene Expression Regulation*
-
Humans
-
Hybridomas
-
Interleukin-2 / biosynthesis*
-
L Cells
-
Membrane Glycoproteins / genetics*
-
Mice
-
Mice, Inbred C57BL
-
Molecular Sequence Data
-
Nuclear Receptor Subfamily 1, Group F, Member 3
-
Receptor-CD3 Complex, Antigen, T-Cell / metabolism
-
Receptors, Cytoplasmic and Nuclear / genetics*
-
Receptors, Retinoic Acid*
-
Receptors, Thyroid Hormone*
-
T-Lymphocytes / metabolism*
-
Tumor Cells, Cultured
Substances
-
DNA, Complementary
-
FASLG protein, human
-
Fas Ligand Protein
-
Fasl protein, mouse
-
Interleukin-2
-
Membrane Glycoproteins
-
Nuclear Receptor Subfamily 1, Group F, Member 3
-
RORC protein, human
-
Receptor-CD3 Complex, Antigen, T-Cell
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Retinoic Acid
-
Receptors, Thyroid Hormone
-
Rorc protein, mouse