IL-4 secreted from individual naive CD4+ T cells acts in an autocrine manner to induce Th2 differentiation

Eur J Immunol. 2002 May;32(5):1428-33. doi: 10.1002/1521-4141(200205)32:5<1428::AID-IMMU1428>3.0.CO;2-0.


Naive CD4(+) T cell populations rapidly produce small amounts of IL-4 in response to T cell receptor-mediated stimulation and may undergo Th2 differentiation without exogenous IL-4. Whether this is due to autocrine IL-4-stimulation or the production of IL-4 by an infrequent naive cell has not been determined. Here we show that single CD4(+) T cells from RAG2-/- T cells receptor transgenic mice primed with their cognate antigen give rise to IL-4-producing cells at a similar frequency whether primed with or without added IL-4, but not if anti-IL-4 is added to the culture. Thus, each founder cell or one or more of its early daughters can produce sufficient IL-4 to drive Th2 differentiation. This indicates that autocrine IL-4 production by naive CD4 T cells can drive the appearance of Th2 cells.

MeSH terms

  • Animals
  • Antigens / administration & dosage
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Clone Cells
  • DNA-Binding Proteins / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Interleukin-4 / genetics
  • Th2 Cells / cytology
  • Th2 Cells / immunology*


  • Antigens
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-4
  • V(D)J recombination activating protein 2
  • Interleukin-4
  • Ovalbumin