Recent evidence has implicated interleukin-7 (IL-7) as a master regulator o
f T-cell homeostasis, based upon its essential role in the homeostatic expa
nsion of naive T-cell populations in response to low-affinity antigens (Ags
) and its capacity to enhance dramatically the expansion of peripheral T-ce
ll populations in response to high-affinity Ags. Furthermore, T-cell-deplet
ed humans have a unique inverse relationship between the peripheral CD4(+)
T-cell count and the level of circulating IL-7. Together, these data sugges
t that increased amounts of IL-7 become available following T-cell depletio
n, thus, enhancing the high- and low-affinity Ag-driven expansion of the po
pulation of residual, mature T cells and boosting thymic regenerative capac
ity, as a means to restore T-cell homeostasis.