A two-step process for cytokine production revealed by IL-4 dual-reporter mice

Immunity. 2005 Oct;23(4):419-29. doi: 10.1016/j.immuni.2005.09.006.


To monitor IL-4 expression at the single-cell level, we generated mice with insertions of different reporter genes into both copies of the Il4 gene that permitted the simultaneous analysis of IL-4 transcripts via GFP and IL-4 protein secretion by use of huCD2. Innate and adaptive cells competent for IL-4 production were marked by GFP, while cells that presently or recently secreted IL-4 additionally displayed huCD2. After challenge with the strictly enteric helminth, Heligmosomoides polygyrus, GFP-positive innate and adaptive cells disseminated widely, but IL-4 secretion was predominantly mediated by CD4+ T cells in the intestines and draining lymphoid organs. IL-4-competent cells persisted in cured animals, and memory responses reflected rapid cytokine production at the site of rechallenge. These data reveal a two-step process for cytokine production: the first generating poised cells that disseminate systemically and the second inducing the rapid production of the cytokine in response to local stimulation.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Helminth
  • CD2 Antigens / metabolism
  • Cytokines / biosynthesis*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics*
  • Green Fluorescent Proteins / immunology*
  • Interleukin-4 / genetics*
  • Interleukin-4 / immunology*
  • Interleukin-4 / metabolism
  • Lymphocytes / immunology
  • Mice
  • Mice, Transgenic
  • Nematospiroides dubius / immunology
  • T-Lymphocytes / immunology


  • Antigens, Helminth
  • CD2 Antigens
  • Cytokines
  • Green Fluorescent Proteins
  • Interleukin-4