Pinpointing IL-4-independent acquisition and IL-4-influenced maintenance of Th2 activity by CD4 T cells

Eur J Immunol. 2004 Mar;34(3):686-694. doi: 10.1002/eji.200324510.


Naive CD4 T cells develop Th2 activity early in primary responses to alum-precipitated proteins by producing IL-4 mRNA and inducing B cells to produce gamma1 and epsilon switch transcripts. Both IL-4-dependent and IL-4-independent pathways for IL-4 induction are recognized, but their relative contribution to the different phases of primary Th2 responses in vivo is uncertain. We show the primary induction of IL-4 synthesis in lymph nodes responding to alum-precipitated protein is overwhelmingly in antigen-specific CD4 T cells and is unimpaired in IL-4Ralpha(-/-) mice, which can produce but do not respond to IL-4 and IL-13. Ig class-switching in extra-follicular responses, reflecting Th2 activity, is also unimpaired in these mice. By contrast, 7 days after immunization--when T cells are selecting B cells in germinal centers and T cell priming has occurred--non-responsiveness to IL-4 is associated with smaller germinal centers, increased levels of T-bet and gamma2a switch transcripts and reduced gamma1 and epsilon transcripts. These data indicate that Th2 characteristics acquired during T cell priming and the initial CD4 T cell interaction with B cells are largely IL-4-independent, whereas IL-4 production induced during priming has a significant role in maintaining the Th2 phenotype as T cells select B cells in germinal centers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Germinal Center / immunology
  • Interleukin-13 / physiology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / physiology*
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Ovalbumin / immunology
  • Receptors, Interleukin-4 / genetics
  • Signal Transduction
  • Th1 Cells / immunology
  • Th2 Cells / immunology*


  • Interleukin-13
  • Receptors, Interleukin-4
  • Interleukin-4
  • Ovalbumin