In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation

Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12423-8. doi: 10.1073/pnas.0806372105. Epub 2008 Aug 21.

Abstract

The expression of interleukin-4 (IL-4) is viewed as the hallmark of a Th2 lymphocyte, whereas the subsequent action of IL-4 and IL-13, mediated through the STAT6 signaling pathway, is seen as a prerequisite for the full development of Th2 immune responses to parasites and allergens. G4 mice, whose IL-4 gene locus contains the fluorescent reporter eGFP, were used to quantify the number of Th2 cells that develop during Nippostrongylus brasiliensis- or allergen-induced immune responses under conditions where IL-4 or STAT6 was absent. Here, we show that deletion of IL-4 or STAT6 had little impact on the number or timing of appearance of IL-4-producing Th2 cells. These data indicate that in vivo differentiation of naïve CD4 T cells to Th2 status often occurs independently of IL-4 and STAT6 and that recently described pathways of Th2 cell differentiation may explain how allergens and parasites selectively induce Th2-mediated immunity.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Cell Differentiation*
  • Immunity*
  • Interleukin-4 / physiology*
  • Mice
  • Mice, Mutant Strains
  • Nippostrongylus / immunology
  • Parasites / immunology
  • STAT6 Transcription Factor / physiology*
  • Signal Transduction*
  • Th2 Cells / cytology*

Substances

  • Allergens
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Interleukin-4