Kruppel-like factor 2 is required for trafficking but not quiescence in postactivated T cells

J Immunol. 2011 Jan 15;186(2):775-83. doi: 10.4049/jimmunol.1000094. Epub 2010 Dec 15.


The transcription factor Kruppel-like factor 2 (KLF2) was proposed to regulate genes involved in cell cycle entry and T cell trafficking; however, the physiological role of its expression in postactivated T cells is not well defined. Previous studies suggested that the cytokines IL-2 and IL-15 differentially regulate KLF2 re-expression in postactivation T cells and that these cytokines also influence effector versus memory T cell differentiation. Using conditional and inducible KLF2-knockout model systems, we tested the specific role of KLF2 expression in activated CD8(+) T cells cultured with these cytokines. KLF2 was required for effective transcription of sphingosine-1-phosphate receptor-1 (S1P(1)) and CD62L in postactivation T cells. However, although different cytokines dramatically altered the expression of cell-cycle-related genes, endogenous KLF2 had a minimal impact. Correspondingly, KLF2-deficient T cells showed dysregulated trafficking but not altered proliferative characteristics following in vivo responses to Ag. Thus, our data help to define KLF2-dependent and -independent aspects of activated CD8(+) T cell differentiation and argue against a physiological role in cell cycle regulation.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / administration & dosage
  • Antigens / immunology
  • Apoptosis / genetics
  • Apoptosis / immunology
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Cycle / genetics
  • Cell Cycle / immunology
  • Cell Migration Inhibition / immunology
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Cells, Cultured
  • Immunologic Memory / genetics
  • Kruppel-Like Transcription Factors / deficiency*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / physiology*
  • L-Selectin / biosynthesis
  • L-Selectin / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / metabolism
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Resting Phase, Cell Cycle / genetics
  • Resting Phase, Cell Cycle / immunology*
  • Time Factors


  • Antigens
  • Klf2 protein, mouse
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Sip1 protein, mouse
  • L-Selectin
  • Ovalbumin