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 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.
Breloer
M
M
Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany. Mbreloer@aol.com
Dorner
B
B
Moré
S H
SH
Roderian
T
T
Fleischer
B
B
von Bonin
A
A
D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000494:pharmacology*; D005057:Eukaryotic Cells / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D037181:Lectins, C-Type; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018834:Chaperonin 60; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D010047:Ovalbumin; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C111390:OVA 323-339