Long-term survival but impaired homeostatic proliferation of naïve T cells in the absence of p56lck

Interactions between the T cell receptor (TCR) and major histocompatibility complex antigens are essential for the survival and homeostasis of peripheral T lymphocytes. However, little is known about the TCR signaling events that result from these interactions. The peripheral T cell pool of p56lck (lck)-deficient mice was reconstituted by the expression of an inducible lck transgene. Continued survival of peripheral naïve T cells was observed for long periods after switching off the transgene. Adoptive transfer of T cells from these mice into T lymphopoienic hosts confirmed that T cell survival was independent of lck but revealed its essential role in TCR-driven homeostatic proliferation of naïve T cells in response to the T cell-deficient host environment. These data suggest that survival and homeostatic expansion depend on different signals.