The interplay between the duration of TCR and cytokine signaling determines T cell polarization

Eur J Immunol. 1999 Dec;29(12):4092-101. doi: 10.1002/(SICI)1521-4141(199912)29:12<4092::AID-IMMU4092>3.0.CO;2-A.


Development of Th1 and Th2 effector lymphocytes is driven primarily by IL-12 or IL-4, but is also influenced by the strength of antigenic stimulation. However, the mechanism by which TCR signaling contributes to T cell polarization remains elusive. We show that in the presence of IL-12 a short TCR stimulation can lead to efficient Th1 polarization and IL-12 exerts its effect when present during, as well as after, TCR signaling. In contrast, Th2 polarization requires a prolonged TCR stimulation and IL-4 is effective only when present during the period of TCR triggering. The simultaneous stimulation by TCR and IL-4 is required to induce demethylation of IL-4 and IL-13 genes that accompanies the stochastic generation of Th2 cells producing either or both cytokines. Thus, the duration of TCR stimulation represents a crucial parameter that influences the response to polarizing cytokines and the acquisition of T cell effector functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Polarity / immunology*
  • Cells, Cultured
  • Cytokines / immunology*
  • Flow Cytometry
  • Lymphocyte Activation / immunology
  • Mice
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology*
  • Th1 Cells / cytology*
  • Th1 Cells / immunology*
  • Th2 Cells / cytology*
  • Th2 Cells / immunology*


  • Cytokines
  • Receptors, Antigen, T-Cell