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

Heat shock proteins (HSP) like Hsp60, Hsp70 and gp96 act directly on antige n-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-gam ma in the absence of antigenic peptide; however, the release of IFN-gamma i s 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 stric tly 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 pre sence of Hsp60. Hsp60-containing OT-1 T cell cultures produced IFN-gamma ev en when the number of antigenic MHC class I complexes was too low to be sti mulatory 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-spe cific T cells.