Ms. Vacchio et al., Thymus-derived glucocorticoids set the thresholds for thymocyte selection by inhibiting TCR-mediated thymocyte activation, J IMMUNOL, 163(3), 1999, pp. 1327-1333
Selection processes in the thymus eliminate nonfunctional or harmful T cell
s and allow the survival of those cells with the potential to recognize Ag
in association with self-MHC-encoded molecules (Ag/MHC). We have previously
demonstrated that thymus-derived glucocorticoids antagonize TCR-mediated d
eletion, suggesting a role for endogenous thymic glucocorticoids in promoti
ng survival of thymocytes following TCR engagement. Consistent with this hy
pothesis, we now show that inhibition of thymus glucocorticoid biosynthesis
causes an increase in thymocyte apoptosis and a decrease in recovery that
are directly proportional to the number of MHC-encoded molecules present an
d, therefore, the number of ligands available for TCR recognition. Expressi
on of CD5 on CD4(+)CB8(+) thymocytes, an indicator of TCR-mediated activati
on, increased in a TCR- and MHC-dependent manner when corticosteroid produc
tion or responsiveness was decreased. These results indicate that thymus-de
rived glucocorticoids determine where the window of thymocyte selection occ
urs in the TCR avidity spectrum by dampening the biological consequences of
TCR occupancy and reveal that glucocorticoids mask the high percentage of
self-Ag/MHC-reactive thymocytes that exist in the preselection repertoire.