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

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Abstract

ABSTRACT

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.

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    This work was supported by funds from the Albert Einstein College of Medicine.

    ☆☆

    Communicated by P. Nowell, M.D.04/10/01

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    Correspondence and reprint requests to: Michael B. Prystowsky. E-mail: [email protected].

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