Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo

J Immunol. 2008 Jul 1;181(1):104-8. doi: 10.4049/jimmunol.181.1.104.


VLA-4 plays a critical role in T cell trafficking into inflammatory sites. Our recent studies have suggested that VLA-4 expression on CD8+ T cells is negatively controlled by IL-4 and serves as a functionally distinguishing variable for why Type-1, but not Type-2, CD8+ T cells are able to traffic into tumors. In this study, using in vitro culture of murine CD8+ T cells under Type-1 and Type-2 cytokine conditions, we show that IL-4-mediated down-regulation of VLA-4 expression is completely abrogated in Stat6-deficient CD8+ T cells. Conversely, CD8+ T cells expressing a constitutively active mutant form Stat6 (Stat6VT) failed to express VLA-4 even in the absence of IL-4-stimulation. Notably, Type-2 CD8+ T cells developed from Stat6-/- but not wild-type mice were competent to migrate into tumor lesions in vivo. These results suggest that Stat6-signaling is necessary and sufficient to restrict CD8+ T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8+ T cell infiltration into tumors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Down-Regulation
  • Integrin alpha4beta1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Transport
  • STAT6 Transcription Factor / deficiency
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism*
  • Signal Transduction / immunology*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Integrin alpha4beta1
  • STAT6 Transcription Factor
  • Vascular Cell Adhesion Molecule-1
  • Phosphatidylinositol 3-Kinases