Heat shock proteins as "danger signals": eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-gamma production in T cells

Eur J Immunol. 2001 Jul;31(7):2051-9. doi: 10.1002/1521-4141(200107)31:7<2051::aid-immu2051>3.0.co;2-h.


The heat shock proteins (HSP) gp96, Hsp70 and Hsp60 activate professional antigen-presenting cells (APC) to secrete proinflammatory cytokines and to express costimulatory molecules. Here, we analyze the impact of Hsp60 as a hypothetical danger signal on the antigen-specific activation of T cells derived from DO11.10 TCR-transgenic mice. The release of IFN-gamma, induced by the antigenic OVA(323-339)-peptide, is increased and accelerated dramatically by the addition of Hsp60 to ex vivo purified populations of T cells and peritoneal macrophages (PEC), while the antigen-specific IL-2 production or proliferation of the T cells remain unchanged. In contrast, "effector" T cells, undergoing secondary stimulation, displayed almost unchanged activation kinetics in the presence of Hsp60. The presence of Hsp60 induces IFN-gamma and up-regulation of CD69 in T cell/PEC cocultures even in the absence of antigenic peptide and this induction of IFN-gamma is strictly dependent on the ability of the macrophages to produce IL-12. Taken together, our data strongly suggest that the presence of eukaryotic mitochondrial Hsp60 allows antigen-specific IFN-gamma secretion under conditions when an antigenic stimulus alone is not sufficient to activate T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Cell Line
  • Cells, Cultured
  • Chaperonin 60 / pharmacology*
  • Eukaryotic Cells / metabolism
  • Interferon-gamma / biosynthesis*
  • Interleukin-2 / biosynthesis
  • Kinetics
  • Lectins, C-Type
  • Macrophages, Peritoneal / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes / immunology*
  • Up-Regulation


  • Antigens
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Chaperonin 60
  • Interleukin-2
  • Lectins, C-Type
  • OVA 323-339
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Interferon-gamma
  • Ovalbumin