Glucocorticoid-mediated repression of T-cell receptor signalling is impaired in glucocorticoid receptor exon 2-disrupted mice.
Studies using glucocorticoid receptor exon 2-disrupted knockout (GR2KO) mice provided strong evidence against an obligatory role for glucocorticoid receptor (GR) signalling in T-cell selection. These mice express a truncated form of the GR that is incapable of transmitting a range of glucocorticoid (GC)-induced signals, including GC-induced thymocyte death. However, one study that suggested that truncated GR function is preserved in the context of GR-mediated repression of T-cell activation-induced genes, challenged earlier conclusions derived from the use of these mice. Because GR versus T-cell receptor (TCR) signalling cross-talk is the means by which GCs are hypothesized to have a role in T-cell selection, we reassessed the utility of GR2KO mice to study the role of the GR in this process. Here, we show that GR-mediated repression of TCR signalling is impaired in GR2KO T cells in terms of TCR-induced activation, proliferation and cytokine production. GC-induced apoptosis was largely abolished in peripheral T cells, and induction of the GC-responsive molecule, interleukin-7 receptor, was also severely reduced in GR2KO thymocytes. Together, these data strongly re-affirm conclusions derived from earlier studies of these mice that the GR is not obligatory for normal T-cell selection.
1] Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia [2] Department of Immunology, Monash University, Victoria, Australia [3] Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
Douglas R
DR
Liddicoat
1] Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia [2] Department of Immunology, Scripps Research Institute, La Jolla, CA USA.
Jared F
JF
Purton
Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
Timothy J
TJ
Cole
Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
Dale I
DI
Godfrey
D000818:Animals; D060966:Clonal Selection, Antigen-Mediated / Q000502:physiology*; D005091:Exons; D005938:Glucocorticoids / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D005938:Glucocorticoids; D011948:Receptors, Antigen, T-Cell; D011965:Receptors, Glucocorticoid