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

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.

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

“…7). HSPs, while playing an important role in the stimulation of innate immunity through TLRs, also activates T cell and B cell lymphocytes Moré et al 2001); moreover, HSPs can directly activate the adaptive immune T lymphocytes in a TLR2-dependent and TLR4-independent manner, while Hsp60 activates B cells via TLR4 recruitment (Zanin-Zhorov et al 2003;Cohen-Sfady et al 2005;Osterloh et al 2008).…”

Expression and Regulation of ST2, an Interleukin-1 Receptor Family Member, in Cardiomyocytes and Myocardial Infarction

“…Nuclease protection assay was performed with a 71-mer oligonucleotide spanning the splice junction of soluble Fit-1S and membrane Fit-1M, which was 3Ј-end labeled with 32 Pdd[␣-ATP] (Amersham) using terminal deoxynucleotidyl transferase. Nuclease-digested hybridized products were electrophoresed through a 5% polyacrylamide gel followed by autoradiography.…”

Hsp60 and Hsp10 as antitumour molecular agents

“…In contrast to CD45RA+ RO-(naive) and CD45RA-RO+ (memory) cells, T cell populations proliferated after stimulation with bacterial Hsp60 from Mycobacterium leprae, Escherichia coli or Chlamydia trachomatis; (4) as human Hsp60 acts not only directly on antigen-presenting cells (APC) by inducing the secretion of cytokines but also on other leucocytes, the impact of Hsp60 on the antigen-specific activation of CD8 + T cells was studied. 20 It was found that Hsp60 enhances the activation of cytotoxic T cells through activated macrophages, thus acting as a molecular link between innate-and adaptativeimmune systems; (5) IL-12 was found to play a central role in Hsp60-mediated IFNg induction, which was dependent on costimulatory signals provided by B7-CD28 cells; 21 (6) peripheral blood lymphocytes (PBL) produced Th1-associated peripheral blood lymphocytes (PBL) produced Th1-associated cytokines, including IFNg and IL-12, spontaneously and in response to stimulation with exogenous HSP60-derived peptide; 22 (7) human Hsp60 acts as a costimulator of the human regulatory T cells (Tregs) CD4 + CD25 int and CD4 + CD25 hi ; 23 (8) Hsp60 inhibited IFNg and TNFa secretion and upregulated IL-10 secretion by activated CD4 + T cells. 23 Hsp60 could very well act as a costimulator of CD8+ lymphocytes, and Hsp60-treated CD4 + CD25 + T cells could regulate CD8 + T cell cytokine secretion.…”