Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction

Nat Commun. 2014 Aug 19;5:4674. doi: 10.1038/ncomms5674.

Abstract

Dendritic cells (DCs) are required for the induction of cytotoxic T cells (CTL). In most tissues, including the lung, the resident DCs fall into two types expressing the integrin markers CD103 and CD11b. The current supposition is that DC function is predetermined by lineage, designating the CD103(+) DC as the major cross-presenting DC able to induce CTL. Here we show that Poly I:C (TLR3 agonist) or R848 (TLR7 agonist) do not activate all endogenous DCs. CD11b(+) DCs can orchestrate a CTL response in vivo in the presence of a TLR7 agonist but not a TLR3 agonist, whereas CD103(+) DCs require ligation of TLR3 for this purpose. This selectivity does not extend to antigen cross-presentation for T-cell proliferation but is required for induction of cytotoxicity. Thus, we demonstrate that the ability of DCs to induce functional CTLs is specific to the nature of the pathogen-associated molecular pattern (PAMP) encountered by endogenous DC.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD11b Antigen / genetics
  • CD11b Antigen / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology*
  • Female
  • Imidazoles / pharmacology
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / metabolism
  • Interleukin-27 / physiology
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Lymphocyte Activation / physiology
  • Male
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Poly I-C / pharmacology
  • Toll-Like Receptor 3 / drug effects
  • Toll-Like Receptor 3 / physiology
  • Toll-Like Receptor 7 / drug effects
  • Toll-Like Receptor 7 / physiology

Substances

  • Antigens, CD
  • CD11b Antigen
  • Imidazoles
  • Integrin alpha Chains
  • Interleukin-27
  • Membrane Glycoproteins
  • TLR3 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • alpha E integrins
  • Poly I-C
  • resiquimod

Associated data

  • GEO/GSE15907