Genetic regulation of commitment to interleukin 4 production by a CD4(+) T cell-intrinsic mechanism

J Exp Med. 1998 Dec 21;188(12):2289-99. doi: 10.1084/jem.188.12.2289.


The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4 expression during differentiation into mature effector cells remain incompletely defined. As compared to cells from most strains of mice, activated CD4(+) T cells from BALB mice show a bias towards IL-4 production and T helper 2 commitment in vitro and in vivo. Here, we show that this bias arises not from an increase in the amount of IL-4 produced per cell, but rather from an increase in the proportion of CD4(+) T cells that commit to IL-4 expression. This strain-specific difference in commitment was independent of signals mediated via the IL-4 receptor and hence occurred upstream of potential autoregulatory effects of IL-4. Segregation analysis of the phenotype in an experimental backcross cohort implicated a polymorphic locus on chromosome 16. Consistent with a role in differentiation, expression of the phenotype was CD4(+) T cell intrinsic and was evident as early as 16 h after the activation of naive T cells. Probabilistic gene activation is proposed as a T cell-intrinsic mechanism capable of modulating the proportion of naive T cells that commit to IL-4 production.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Chimera / genetics
  • Chimera / immunology
  • Crosses, Genetic
  • Genetic Linkage
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics*
  • Interleukin-4 / immunology
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • Interleukins / immunology
  • L-Selectin / analysis
  • Liver / cytology
  • Liver / embryology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred Strains
  • Phenotype
  • Polymorphism, Genetic
  • RNA, Messenger / analysis
  • Receptors, Interleukin-4 / antagonists & inhibitors
  • Receptors, Interleukin-4 / physiology
  • Signal Transduction
  • Spleen / cytology
  • Th2 Cells / cytology
  • Th2 Cells / immunology


  • Interleukins
  • RNA, Messenger
  • Receptors, Interleukin-4
  • L-Selectin
  • Interleukin-4