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TLR2 engagement on dendritic cells promotes high frequency effector and memory CD4 T cell responses

Academic Article
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Overview

authors

  • Chandran, S. S.
  • Verhoeven, D.
  • Teijaro, John R.
  • Fenton, M. J.
  • Farber, D. L.

publication date

  • December 2009

journal

  • Journal of Immunology  Journal

abstract

  • Ligation of TLR by distinct pathogen components provides essential signals for T cell priming, although how individual TLR engagement affects primary and memory T cell responses is not well defined. In this study, we demonstrate distinct effects of TLR2 vs TLR4 engagement on primary and memory CD4 T cell responses due to differential effects on APC. Priming of influenza hemagglutinin (HA)-specific naive CD4 T cells with HA peptide and the TLR2 agonist Pam3CysK in vivo resulted in a high frequency of activated HA-specific CD4 T cells that predominantly produced IL-2 and IL-17, whereas priming with HA peptide and the TLR4 agonist LPS yielded a lower frequency of HA-specific CD4 T cells and predominant IFN-gamma producers. TLR2 agonist priming depended on TLR2 expression by APC, as wild-type CD4 T cells did not expand in response to peptide and Pam3CysK in TLR2-deficient hosts. TLR2-mediated priming also led to an increased frequency of Ag-specific memory CD4 T cells compared with TLR4 priming and mediated enhanced secondary responses to influenza challenge. Our results show that TLR engagement on APC influences both primary and secondary CD4 T cell responses, and suggest that long-term functional capacities of T cells are set by innate signals during early phases of an infection.

subject areas

  • Animals
  • Antigen-Presenting Cells
  • CD4-Positive T-Lymphocytes
  • Dendritic Cells
  • Dogs
  • Epitopes, T-Lymphocyte
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunity, Innate
  • Immunologic Memory
  • Influenza A virus
  • Lymphocyte Activation
  • Mice
  • Mice, Congenic
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Orthomyxoviridae Infections
  • Signal Transduction
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.0901683

PubMed ID

  • 19933854
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Additional Document Info

start page

  • 7832

end page

  • 7841

volume

  • 183

issue

  • 12

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