T-Cell-Receptor-Dependent Signal Intensity Dominantly Controls CD4+ T Cell Polarization InVivo

Nicholas J. Van Panhuys, Frederick Klauschen, RonaldN Germain

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Polarization of effector CD4+ Tcells can be influenced by both antigen-specific signals and by pathogen- oradjuvant-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+ Tcell interactions with dendritic cells (DCs) exposed to polarizing adjuvants. These studies revealed a close correspondence between strength of Tcell receptor (TCR)-dependent signaling and T helper 1 (Th1) versus Th2 cell fate, with antigen concentration dominating over adjuvant in controlling Tcell polarity. Consistent with this finding, at afixed 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.

Original languageEnglish
Pages (from-to)63-74
Number of pages12
JournalImmunity
Volume41
Issue number1
DOIs
Publication statusPublished - 17 Jul 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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