Liver-primed Memory T Cells Generated Under Noninflammatory Conditions Provide Anti-Infectious Immunity

Cell Rep. 2013 Mar 28;3(3):779-95. doi: 10.1016/j.celrep.2013.02.008. Epub 2013 Mar 14.

Abstract

Development of CD8(+) T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1(+) memory population. Generation of liver-primed memory T cells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD28 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cross-Priming
  • Dendritic Cells / immunology
  • Endothelial Cells / immunology
  • Gene Expression Profiling
  • Immunity, Innate
  • Immunologic Memory*
  • Listeria monocytogenes / immunology
  • Liver / cytology
  • Liver / immunology*
  • Liver / microbiology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-12 / immunology

Substances

  • CD28 Antigens
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-12
  • Neuropilin-1

Associated data

  • GEO/GSE27139