Eukaryotic heat shock proteins as molecular links in innate and adaptive immune responses: Hsp60-mediated activation of cytotoxic T cells

Int Immunol. 2001 Sep;13(9):1121-7. doi: 10.1093/intimm/13.9.1121.

Abstract

Heat shock proteins (HSP) like Hsp60, Hsp70 and gp96 act directly on antigen-presenting cells (APC), e.g. by inducing the secretion of cytokines. Here we analyzed the impact of Hsp60 on the antigen-specific activation of CD8(+) T cells in a TCR transgenic system. Hsp60 induced low amounts of IFN-gamma in the absence of antigenic peptide; however, the release of IFN-gamma is increased by a factor of 3-10 following the addition of Hsp60 to purified populations of OT-1 [ovalbumin (OVA)257-264/H2-K(b)-restricted] T cells and antigen-pulsed peritoneal exudate cells (PEC) as APC. This effect is strictly correlated with the PEC ability to produce IL-12. In contrast, antigen-specific IL-2 secretion and T cell proliferation was not changed in the presence of Hsp60. Hsp60-containing OT-1 T cell cultures produced IFN-gamma even when the number of antigenic MHC class I complexes was too low to be stimulatory and could not be detected with specific mAb. Hsp60, thus, acts as a catalyzing molecule to initiate both innate and adaptive immune responses, and its presence (e.g. during an infection with cellular destruction) has direct consequences for the activation of otherwise 'ignorant' antigen-specific T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Chaperonin 60 / genetics
  • Chaperonin 60 / immunology*
  • Eukaryotic Cells
  • Humans
  • Interferon-gamma / metabolism*
  • Interleukin-12 / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Chaperonin 60
  • Receptors, Antigen, T-Cell
  • Interleukin-12
  • Interferon-gamma