Early maturation of T-cell progenitors in the absence of glucocorticoids.
In the present work, we demonstrated that both fetal liver and thymic T-cell precursors express glucocorticoid receptors (GRs) indirectly suggesting a role for glucocorticoids (GCs) in the earliest events of T-cell differentiation. To evaluate this issue, we analyzed the thymic ontogeny in the progeny of adrenalectomized pregnant rats (Adx fetuses), an in vivo experimental model, which ensures the absence of circulating GCs until the establishment of the fetal hypothalamus-pituitary-adrenal (HPA) axis. In the absence of maternal GCs, T-cell development was significantly accelerated, the process being reversed by in vivo GC replacement. Mature single positive thymocytes (both CD4 and CD8) appeared in 16-day old fetal Adx thymus when in the control fetuses, most thymocytes still remained in the double-negative (DN) CD4(-)CD8(-) cell compartment. In addition, emigration of T-cell receptor (TcR)alphabeta positive cells to the spleen also occurred earlier in Adx fetuses than in control ones. In vitro recolonization of cultured deoxiguanosine-treated mouse fetal thymus lobes with 13-day-old fetal liver cell suspensions from both Adx and control fetuses demonstrated changes in the developmental capabilities of fetal liver T-cell precursors from embryos grown in the absence of GCs. Furthermore, a precocious lymphoid colonization of the thymic primordium from Adx fetuses was evidenced by ultrastructural analysis of both Adx and Sham early thymus. Both findings accounted for the accelerated T-cell differentiation observed in Adx fetuses. Together, these results support a role for GCs not only in the thymic cell death, but also in the early steps of T-cell differentiation.
Sacedón
R
R
Department of Cell Biology, Faculty of Biology and Medicine, Complutense University, Madrid, Spain.
Vicente
A
A
Varas
A
A
Jiménez
E
E
Muñoz
J J
JJ
Zapata
A G
AG
D000315:Adrenalectomy; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000276:immunology; D005865:Gestational Age; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000276:immunology; D051379:Mice; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology
D011965:Receptors, Glucocorticoid; D003345:Corticosterone