A heat shock protein gene (Hsp70.1) is critically involved in the generation of the immune response to myelin antigen.
Protracted inflammation has been associated with the generation of autoimmune responses. In this respect, increase in the chaperonin, heat shock protein 70 (hsp70) is an outcome of prolonged inflammatory stress. Previous experiments have shown that overexpression of inducible hsp70 in vitro enhanced myelin autoantigen recognition. To prove the role of hsp70 in myelin-directed responses in vivo, we applied a mouse deficient in the major gene encoding inducible hsp70, hsp70.1. Hsp70.1(-/-) mice sensitized for experimental autoimmune encephalomyelitis (EAE) with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, displayed almost complete resistance to the disease. This correlated with the loss of T cell proliferation and IFN-gamma production in response to MOG(35-55). T cell transfer experiments as well as antigen presentation assays in vitro demonstrated that hsp70 deficiency was associated with dysfunction in the activation of autoreactive T cells. Moreover, T cell responses to ovalbumin (OVA) peptide 323-339 were altered and CD4(+) T cells were more prone to TCR-induced apoptosis, suggesting broader spectrum of T cell defect in hsp70.1(-/-) mice. These results provide compelling evidence for generalized effect mediated by inducible hsp70 in the recognition of myelin self and non-self antigens that influences the cytokine profile of the immune response affecting autoimmune demyelination.
Mycko
Marcin P
MP
Department of Neurology, Laboratory of Neuroimmunology, Medical University of Lodz, 22 Kopcinskiego Street, Lodz, Poland.
Cwiklinska
Hanna
H
Walczak
Agata
A
Libert
Claude
C
Raine
Cedric S
CS
Selmaj
Krzysztof W
KW
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; C111390:OVA 323-339; D010446:Peptide Fragments; C081884:heat-shock protein 70.1; D007371:Interferon-gamma; D010047:Ovalbumin