The interplay between the duration of TCR and cytokine signaling determines T cell polarization.
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.
Iezzi
G
G
Basel Institute for Immunology, Basel, Switzerland. lezzi@bii.ch
Scotet
E
E
Scheidegger
D
D
Lanzavecchia
A
A
D000818:Animals; D016764:Cell Polarity / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology*
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell