Naive T cells proliferate independently of cognate antigen when
introduced into lymphopenic hosts. Lymphopenia-induced proliferation
depends on low-affinity MHC/self-peptide complexes and on IL-7.
To elucidate the intracellular signals mediating this proliferation,
we analyzed changes in gene expression in naive CD8+ T cells at
different times after their transfer into a lymphopenic environment.
The genes induced in response to lymphopenia were largely an attenuated
subset of those turned up by full antigenic stimulation, including
genes related to cell cycling, whereas excluding genes specifically
associated with effector activity. After the initial phase of
proliferation in an empty compartment, the naive T cells adopted
a stable pattern of gene expression similar to that of antigen-experienced
memory cells. Thus, T cells proliferating in lymphopenic hosts
do not exhibit a unique gene-expression profile, instead relying
on "traditional" signals for this antigen-independent proliferation;
this process ultimately results in differentiation to "authentic"
memory cells.