Identification of LKLF-regulated genes in quiescent CD4+ T lymphocytes

Mol Immunol. 2005 Mar;42(5):627-41. doi: 10.1016/j.molimm.2004.09.012.

Abstract

The transcription factor LKLF (lung Krüppel-like factor) is expressed at high levels in quiescent CD4+ and CD8+ T lymphocytes and provides an important role in establishment and maintenance of the quiescent state. To identify LKLF-regulated genes, we performed microarray analysis using an established Jurkat T cell line containing a tetracycline-inducible LKLF. LKLF induction in this Jurkat T cell line generates a quiescent phenotype that resembles memory CD4+ T lymphocytes. We found that LKLF induction in Jurkat cells resulted in up-regulation (>1.5-fold) of about 100 mRNAs, while it repressed (>1.5-fold) a similar number of mRNAs. A striking feature of the LKLF-stimulated mRNAs was that a significant number of them encode cell surface proteins or proteins implicated in initiating and propagating cellular signaling cascades. The data suggests that LKLF may establish a phenotype that primes quiescent cells for responses to specific extracellular stimuli. The mRNAs encoding CDw52, IL-10R alpha and paxillin were among the most highly induced transcripts in Jurkat T cells, and we observed that the encoded proteins are down-regulated following activation of quiescent CD4+ T cells isolated from healthy blood donors. We also examined whether LKLF-induced quiescence in Jurkat cells could silence transcription of integrated HIV-1 proviruses. We found however that LKLF-induced quiescence is not sufficient to repress expression of HIV-1 proviruses in Jurkat T cells, suggesting that the HIV-1 provirus is resistant to LKLF-regulated quiescence.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, Neoplasm / genetics
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD52 Antigen
  • Cytoskeletal Proteins / genetics
  • DNA / genetics
  • Gene Expression Regulation*
  • Glycoproteins / genetics
  • HIV Long Terminal Repeat
  • Humans
  • In Vitro Techniques
  • Jurkat Cells
  • Kruppel-Like Transcription Factors
  • Oligonucleotide Array Sequence Analysis
  • Paxillin
  • Phosphoproteins / genetics
  • RNA, Messenger / genetics
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-10
  • Resting Phase, Cell Cycle
  • Trans-Activators / metabolism*

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • Cytoskeletal Proteins
  • Glycoproteins
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • PXN protein, human
  • Paxillin
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Trans-Activators
  • DNA