Intrathymic T cell development and selection proceeds normally in the absence of glucocorticoid receptor signaling.
Glucocorticoids are believed to play a role in T cell development and selection, although their precise function is controversial. Glucocorticoid receptor (GR)-deficient mice were used to directly investigate this problem. GR-deficient thymocytes were resistant to dexamethasone-mediated apoptosis, confirming the absence of glucocorticoid responsiveness. An absence of GR signaling had no impact on thymocyte development either in vivo or in vitro. T cell differentiation, including positive selection, was normal as assessed by normal development of CD4+CD8+, alphabetaTCR+CD4+, and alphabetaTCR+CD8+ thymocytes. Negative selection, mediated by the superantigen staphylococcal enterotoxin B (SEB), or anti-CD3/CD28, was also normal in the absence of GR signaling. In contrast to earlier reports, these data demonstrate that GR signaling is not essential for intrathymic T cell development or selection.
Purton
J F
JF
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
Boyd
R L
RL
Cole
T J
TJ
Godfrey
D I
DI
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018390:Gene Targeting; D005938:Glucocorticoids / Q000502:physiology; D051379:Mice; D009924:Organ Culture Techniques; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000502:physiology*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid