Glucocorticoid receptor deficient thymic and peripheral T cells develop normally in adult mice.
The involvement of glucocorticoid receptor (GR) signaling in T cell development is highly controversial, with several studies for and against. We have previously demonstrated that GR(-/-) mice, which usually die at birth because of impaired lung development, exhibit normal T cell development, at least in embryonic mice and in fetal thymus organ cultures. To directly investigate the role of GR signaling in adult T cell development, we analyzed the few GR(-/-) mice that occasionally survive birth, and irradiated mice reconstituted with GR(-/-) fetal liver precursors. All thymic and peripheral T cells, as well as other leukocyte lineages, developed and were maintained at normal levels. Anti-CD3-induced cell death of thymocytes in vitro, T cell repertoire heterogeneity and T cell proliferation in response to anti-CD3 stimulation were normal in the absence of GR signaling. Finally, we show that metyrapone, an inhibitor of glucocorticoid synthesis (commonly used to demonstrate a role for glucocorticoids in T cell development), impaired thymocyte development regardless of GR genotype indicating that this reagent inhibits thymocyte development in a glucocorticoid-independent fashion. These data demonstrate that GR signaling is not required for either normal T cell development or peripheral maintenance in embryonic or adult mice.
Purton
Jared F
JF
Monash University Medical School, Department of Pathology and Immunology, Victoria, Australia.
Zhan
Yifan
Y
Liddicoat
Douglas R
DR
Hardy
Charles L
CL
Lew
Andrew M
AM
Cole
Timothy J
TJ
Godfrey
Dale I
DI
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D016332:Fetal Tissue Transplantation; D022781:Hepatocytes / Q000166:cytology / Q000637:transplantation; D066298:In Vitro Techniques; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D011965:Receptors, Glucocorticoid; D008797:Metyrapone