Early maturation of T-cell progenitors in the absence of glucocorticoids

In the present work, we demonstrated that both fetal liver and thymic T-cel l precursors express glucocorticoid receptors (GRs) indirectly suggesting a role for glucocorticoids (GCs) in the earliest events of T-cell differenti ation. To evaluate this issue, we analyzed the thymic ontogeny in the proge ny of adrenalectomized pregnant rats (Adx fetuses), an in vivo experimental model, which ensures the absence of circulating GCs until the establishmen t of the fetal hypothalamus-pituitary-adrenal (HPA) axis. In the absence of maternal GCs, T-cell development was significantly accelerated, the proces s being reversed by in vivo GC replacement. Mature single positive thymocyt es (both CD4 and CD8) appeared in 16-day old fetal Adx thymus when in the c ontrol fetuses, most thymocytes still remained in the double-negative (DN) CD4(-)CD8(-) cell compartment. In addition, emigration of T-cell receptor ( TcR)alpha beta positive cells to the spleen also occurred earlier in Adx fe tuses than in control ones. In vitro recolonization of cultured deoxiguanos ine-treated mouse fetal thymus lobes with 13-day-old fetal liver cell suspe nsions from both Adx and control fetuses demonstrated changes in the develo pmental 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 analys is of both Adx and Sham early thymus. Both findings accounted for the accel erated T-cell differentiation observed in Adx fetuses. Together, these resu lts support a role for GCs not only in the thymic cell death, but also in t he early steps of T-cell differentiation. (C) 1999 by The American Society of Hematology.