Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2819-2826
Early Maturation of T-Cell Progenitors in the Absence of
Glucocorticoids
Rosa Sacedón,
Angeles Vicente,
Alberto Varas,
Eva Jiménez,
Juan José Muñoz, and
Agustín G. Zapata
From the Department of Cell Biology, Faculty of Biology and Medicine,
Complutense University, Madrid, Spain.
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)
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.
