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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)572-585
Number of pages14
JournalBlood Cells, Molecules, and Diseases
Volume27
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Sirolimus
Interleukin-2
Cell Survival
Cell Cycle
T-Lymphocytes
Gene Expression
Cell Proliferation
Antigens
cdc Genes
Cell Cycle Checkpoints
Cellular Immunity
Cell Death
Down-Regulation
Complementary DNA

Keywords

  • cDNA microarray
  • IL-2
  • Rapamycin
  • T lymphocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

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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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AU - Harris, Thomas M.

AU - Childs, Geoffrey J.

AU - Prystowsky, Michael B.

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AB - 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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