Glucocorticoid receptor deficient thymic and peripheral T cells develop normally in adult mice
- Author(s)
- Purton, JF; Zhan, YF; Liddicoat, DR; Hardy, CL; Lew, AM; Cole, TJ; Godfrey, DI;
- Details
- Publication Year 2002-12,Volume 32,Issue #12,Page 3546-3555
- Journal Title
- EUROPEAN JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- THYMOCYTE DEVELOPMENT; POSITIVE SELECTION; TRANSGENIC MICE; NEGATIVE SELECTION; INDUCED APOPTOSIS; REPERTOIRE; RESISTANCE; PATHWAYS; DISRUPTION; INHIBITION
- Publisher's Version
- https://doi.org/10.1002/1521-4141(200212)32:12<3546::AID-IMMU3546>3.0.CO;2-S
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-12-01 12:00:00