Macrophages as main inducers of IFN-gamma in T cells following administration of human and mouse heat shock protein 60.
Human Hsp60 (hHsp60) elicits a potent pro-inflammatory response in cells of the innate immune system. Here we compared the capacity of peritoneal exudate cells (PEC) and bone marrow-derived dendritic cells (DC) to stimulate murine T cells in the presence of Hsp60. Hsp60 induced a specific secretion of high amounts of IFN-gamma in T cells with PEC as antigen-presenting cells (APC). Although DC are highly efficient APC, they were much less potent as inducers of IFN-gamma in the presence of Hsp60. The IFN-gamma-inducing effect of Hsp60 is dependent on co-stimulatory signals provided by B7-CD28 interactions. In addition to hHsp60, we used syngenic murine recombinant Hsp60 (mHsp60) and show that mHsp60 also induces IFN-gamma in TCR transgenic T cells. These results demonstrate that mHsp60 as an endogenous 'self' molecule can induce an inflammatory response. Interestingly, mHsp60, although sharing >98% protein sequence identity with the hHsp60 homologue, does not bind to human CD14 molecules. Taken together, our results indicate a finely tuned activation of cells from the innate and adaptive immune system by 'self' Hsp60 that depends strongly on the type of APC.
Breloer
Minka
M
Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht Strasse 74, 20359 Hamburg, Germany.
Moré
Solveig H
SH
Osterloh
Anke
A
Stelter
Felix
F
Jack
Robert S
RS
Bonin Av
Arne von
Av
D000818:Animals; D001854:Bone Marrow Cells; D016466:CHO Cells; D002460:Cell Line; D018834:Chaperonin 60 / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D006224:Cricetinae; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D018834:Chaperonin 60; D018950:Lipopolysaccharide Receptors; D007371:Interferon-gamma