Prevention of Autoimmune Lysis by T Cells with Specificity for a Heat Shock Protein by Antisense Oligonucleotide Treatment

T lymphocytes with specificity for the bacterial heat shock protein (hsp) 60 recognize stressed host cells, thus possibly promoting pathogenesis of certain infectious and autoimmune diseases. Here, we show that autoimmune destruction of stressed Schwann cells and macrophages by cytotoxic T lymphocyt...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-05, Vol.91 (11), p.5085-5088
Main Authors: Steinhoff, Ulrich, Zugel, Ulrich, Wand-Wurttenberger, Angela, Hengel, Hartmut, Rosch, Rudi, Munk, Martin E., Stefan H. E. Kaufmann
Format: Article
Language:English
Subjects:
Animals
Autoimmunity - drug effects
Base Sequence
Cells, Cultured
Cellular biology
Chaperonin 60
Cultured cells
DNA
Heat shock proteins
Heat-Shock Proteins - biosynthesis
Heat-Shock Proteins - immunology
Immunity (Disease)
Immunoprecipitation
Infections
Macrophages
Macrophages - cytology
Macrophages - immunology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligonucleotides, Antisense - pharmacology
Precipitin Tests
Proteins
Schwann cells
Schwann Cells - cytology
Schwann Cells - immunology
T lymphocytes
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Transplantation immunology
Viruses
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Description
Summary:T lymphocytes with specificity for the bacterial heat shock protein (hsp) 60 recognize stressed host cells, thus possibly promoting pathogenesis of certain infectious and autoimmune diseases. Here, we show that autoimmune destruction of stressed Schwann cells and macrophages by cytotoxic T lymphocytes raised against mycobacterial hsp60 can be inhibited by the use of hsp60-specific antisense oligodeoxynucleotides (A-ODNs). The inhibitory effect of hsp60 A-ODNs was specific because lysis of murine cytomegalovirus-infected host cells by virus-specific cytotoxic lymphocytes was not affected. Immunoblot analysis and immunoprecipitation studies suggest that different forms of stress increase hsp60 synthesis in Schwann cells and that this neosynthesis is reduced by hsp60 A-ODNs. These findings (i) provide evidence for participation of endogenous hsp60 in the recognition of stressed host cells by mycobacterial hsp60-crossreactive T cells and (ii) suggest the feasibility of inhibiting autoimmune reactions by target-cell treatment with specific A-ODNs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.11.5085