Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo

Nat Med. 2003 Dec;9(12):1469-76. doi: 10.1038/nm962. Epub 2003 Nov 16.

Abstract

Pathogens or pathogen-associated molecular patterns can signal to cells of the innate immune system and trigger effective adaptive immunity. However, relatively little is known about how the innate immune system detects tissue injury or necrosis. Evidence suggests that the release of heat-shock proteins (HSPs) may provide adjuvant-like signals, but the ability of HSPs to promote activation or tolerance in vivo has not been addressed. In this study we show that Hsp70 promotes dendritic cell (DC) function and, together with antigen, triggers autoimmune disease in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Autoimmunity
  • Base Sequence
  • CD40 Antigens / metabolism
  • DNA, Complementary / genetics
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / immunology
  • HSP70 Heat-Shock Proteins / immunology*
  • Humans
  • Immune Tolerance
  • In Vitro Techniques
  • Interleukin-12 / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Recombinant Proteins / immunology
  • Signal Transduction
  • T-Lymphocytes / immunology*

Substances

  • CD40 Antigens
  • DNA, Complementary
  • HSP70 Heat-Shock Proteins
  • Recombinant Proteins
  • Interleukin-12