Rapamycin Blocks IL-2-Driven T Cell Cycle Progression While Preserving T Cell Survival,

Effective cellular immune responses require increases in antigen-specific T lymphocytes; IL-2 drives antigen-stimulated T cell proliferation and is largely responsible for the increases observed. We used microarrays containing 9000 mouse cDNAs to study IL-2-induced gene expression. IL-2 induces the expression of genes that regulate cell cycle progression, control cell survival, and increase synthetic and metabolic processes during proliferation. IL-2 also suppresses expression of genes that block cell cycle progression and promote cell death. Rapamycin inhibits IL-2-driven proliferation by downregulating the expression of genes required for key processes required for cell cycle progression. Rapamycin also preserves cell survival by keeping intact the IL-2-induced cell survival programs. These complex multifaceted programs of gene expression permit a dynamic regulation of cellular proliferation and cellular survival.