Rapamycin blocks IL-2-driven T cell cycle progression while preserving T cell survival

Blood Cells Mol Dis. 2001 May-Jun;27(3):572-85. doi: 10.1006/bcmd.2001.0420.

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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Culture Techniques
  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Cell Line
  • Cell Survival / drug effects
  • Drug Interactions
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Protein Biosynthesis / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sirolimus / pharmacology*
  • Spleen / cytology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects*

Substances

  • Immunosuppressive Agents
  • Interleukin-2
  • Sirolimus