Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation

In a depleted lymphoid compartment, naive T cells begin a slow proliferatio n that is independent of cognate antigen yet requires recognition of major histocompatibility complex-bound self-peptides. We have followed the phenot ypic and functional changes that occur when naive CD8(+) T cells undergo th is type of expansion in a lymphopenic environment. Naive T cells undergoing homeostasis-driven proliferation convert to a phenotypic and functional st ate similar to that of memory T cells, yet distinct from antigen-activated effector T cells. Naive T cells dividing in a lymphopenic host upregulate C D44, CD122 (interleukin 2 receptor beta) and Ly6C expression, acquire the a bility to rapidly secrete interferon gamma, and become cytotoxic effecters when stimulated with cognate antigen. The conversion of naive T cells to ce lls masquerading as memory cells in response to a homeostatic signal does n ot represent an irreversible differentiation. Once the cellularity of the l ymphoid compartment is restored and the T cells cease their division, they regain the functional and phenotypic characteristics of naive T cells. Thus , homeostasis-driven proliferation provides a thymus-independent mechanism for restoration of the naive compartment after a loss of T cells.