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 la rgely responsible for the increases observed. We used microarrays containin g similar to 9000 mouse cDNAs to study IL-2-induced gene expression. IL-2 i nduces the expression of genes that regulate cell cycle progression, contro l cell survival, and increase synthetic and metabolic processes during prol iferation. IL-2 also suppresses expression of genes that block cell cycle p rogression and promote cell death. Rapamycin inhibits IL-2-driven prolifera tion by downregulating the expression of genes required for key processes r equired for cell cycle progression. Rapamycin also preserves cell survival by keeping intact the IL-2-induced cell survival programs. These complex mu ltifaceted programs of gene expression permit a dynamic regulation of cellu lar proliferation and cellular survival. (C) 2001 Academic Press.