T-cell-receptor-dependent signal intensity dominantly controls CD4(+) T cell polarization In Vivo

Immunity. 2014 Jul 17;41(1):63-74. doi: 10.1016/j.immuni.2014.06.003. Epub 2014 Jun 26.


Polarization of effector CD4(+) T cells can be influenced by both antigen-specific signals and by pathogen- or adjuvant-induced cytokines, with current models attributing a dominant role to the latter. Here we have examined the relationship between these factors in shaping cell-mediated immunity by using intravital imaging of CD4(+) T cell interactions with dendritic cells (DCs) exposed to polarizing adjuvants. These studies revealed a close correspondence between strength of T cell receptor (TCR)-dependent signaling and T helper 1 (Th1) versus Th2 cell fate, with antigen concentration dominating over adjuvant in controlling T cell polarity. Consistent with this finding, at a fixed antigen concentration, adjuvants inducing Th1 cells operated by affecting DC costimulation that amplified TCR signaling. TCR signal strength controlled downstream cytokine receptor expression, linking the two components in a hierarchical fashion. These data reveal how quantitative integration of antigen display and costimulation regulates downstream checkpoints responsible for cytokine-mediated control of effector differentiation.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adoptive Transfer
  • Animals
  • Calcium Signaling / immunology
  • Cell Communication / immunology*
  • Cell Differentiation / immunology
  • Cell Polarity / immunology*
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Transgenic
  • Papain / pharmacology
  • Receptors, Antigen, T-Cell / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Adjuvants, Immunologic
  • Cytokines
  • Lipopolysaccharides
  • Receptors, Antigen, T-Cell
  • Papain