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

The heat shock proteins (HSP) gp96, Hsp70 and Hsp60 activate professional a ntigen-presenting cells (APC) to secrete proinflammatory cytokines and to e xpress costimulatory molecules. Here, we analyze the impact of Hsp60 as a h ypothetical danger signal on the antigen-specific activation of T cells der ived from DO11.10 TCR-transgenic mice. The release of IFN-gamma, induced by the antigenic OVA(323-339)-peptide, is increased and accelerated dramatica lly by the addition of Hsp60 to ex vivo purified populations of T cells and peritoneal macrophages (PEC), while the antigen-specific IL-2 production o r proliferation of the T cells remain unchanged. In contrast, "effector" T cells, undergoing secondary stimulation, dis played almost unchanged activa tion kinetics in the presence of Hsp60. The presence of Hsp60 induces IFN-g amma 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 da ta strongly suggest that the presence of eukaryotic mitochondrial Hsp60 all ows antigen-specific IFN-gamma secretion under conditions when an antigenic stimulus alone is not sufficient to activate T cells.