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

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

Author information

1
Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: vanpanhuysn@niaid.nih.gov.
2
Institute of Pathology, Charité University Hospital, 10117 Berlin, Germany.
3
Lymphocyte Biology Section, Laboratory of Systems Biology, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: rgermain@niaid.nih.gov.

Abstract

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.

PMID:
24981853
PMCID:
PMC4114069
DOI:
10.1016/j.immuni.2014.06.003
[Indexed for MEDLINE]
Free PMC Article

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