Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis.
Heat shock proteins (Hsp) are markedly up-regulated at sites of inflammation during autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of mice with EAE prevented the development of EAE clinically and pathologically when administered before proteolipid protein 139-151 (PLP139-151) immunization. In contrast, pure Hsp70 or Hsp70-pc derived from brains of healthy mice or other inflamed tissue did not modulate the expression of EAE. In animals in which EAE had been suppressed by Hsp70-pc, lymphocytes showed increased cell death in response to PLP139-151 that correlated with elevated IFN-gamma and NO production. Coculture of spleen cells from Hsp70-pc immunized mice with spleen cells from untreated EAE mice, in addition to depletion experiments, showed that NK cells reduced reactivity to PLP139-151. Transfer of NK cells from Hsp70-pc-immunized mice to recipients sensitized for EAE abolished disease development. Thus, we propose that Hsp70 demonstrate the ability to bind to peptides generated during brain inflammation and to induce a regulatory NK cell population that is capable of preventing subsequent autoimmunization for EAE.
Galazka
Grazyna
G
Department of Neurology, Medical University of Lodz, Lodz, Poland.
Stasiolek
Mariusz
M
Walczak
Agata
A
Jurewicz
Anna
A
Zylicz
Alicja
A
Brosnan
Celia F
CF
Raine
Cedric S
CS
Selmaj
Krzysztof W
KW
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D018840:HSP70 Heat-Shock Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D010455:Peptides; C435023:myelin proteolipid protein (139-151); D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma