Ligand-induced autoregulation of IFN-gamma receptor beta chain expression in T helper cell subsets.
Interferon gamma (IFN-gamma) responsiveness in certain cells depends on the state of cellular differentiation or activation. Here an in vitro developmental system was used to show that IFN-gamma produced during generation of the CD4+ T helper cell type 1 (TH1) subset extinguishes expression of the IFN-gamma receptor beta subunit, resulting in TH1 cells that are unresponsive to IFN-gamma. This beta chain loss also occurred in IFN-gamma-treated TH2 cells and thus represents a specific response of CD4+ T cells to IFN-gamma rather than a TH1-specific differentiation event. These results define a mechanism of cellular desensitization where a cytokine down-regulates expression of a receptor subunit required primarily for signaling and not ligand binding.
Bach
E A
EA
Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Szabo
S J
SJ
Dighe
A S
AS
Ashkenazi
A
A
Aguet
M
M
Murphy
K M
KM
Schreiber
R D
RD
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D015870:Gene Expression; D005805:Genes, MHC Class I; D007371:Interferon-gamma / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000096:biosynthesis*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D016207:Cytokines; D007371:Interferon-gamma; D008024:Ligands; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor