IL-12 enhances CD8 T cell homeostatic expansion

The size of the T lymphocyte pool is maintained by regulation of T cell pro duction, proliferation, and survival. Under the pressure of a T lymphopenic environment, mature naive T cells begin to proliferate in the absence of A g, a process called homeostatic expansion. Homeostatic expansion involves T CR recognition of self peptide/MHC ligands, but less is known about the sol uble factors that regulate this process. Here we show that IL-12 dramatical ly enhanced the homeostatic proliferation of CD8 T cells. In contrast, IL-2 had no beneficial effect on homeostatic expansion and, in fact. inhibited T cell expansion induced by IL-12. Using gene-targeted mice, we showed that IL-12 acted directly on the T cells to enhance homeostatic expansion, but that IL-12 cannot override the requirement for TCR interaction with self pe ptide/MHC ligands in homeostatic expansion. These data indicate that inflam matory cytokines may modulate T cell homeostasis after lymphopenia and have implications for regulation of the T cell repertoire and autoimmunity.