The naive and memory T lymphocyte pools are maintained through poorly under
stood homeostatic mechanisms that may include signaling via cytokine recept
ors. We show that interleukin-7 (IL-7) plays multiple roles in regulating h
omeostasis of CD8(+) T cells. We found that IL-7 was required for homeostat
ic expansion of naive CD8(+) and CD4(+) T cells in lymphopenic hosts and fo
r CD8(+) T cell survival in normal hosts. In contrast, IL-7 was not necessa
ry for growth of CD8(+)T cells in response to a virus infection but was cri
tical for generating T cell memory. Up-regulation of Bcl-2 in the absence o
f IL-7 signaling was impaired after activation in vivo. Homeostatic prolife
ration of memory cells was also partially dependent on IL-7. These results
point to IL-7 as a pivotal cytokine in T cell homeostasis.