Autoimmunity to heat shock protein 60 and antigen-specific production of interleukin-10.
The immunopathologic sequelae of chlamydial infection are correlated with immune responses to the Chlamydia trachomatis heat shock protein 60 (hsp60). One pathogenic mechanism that may explain this association is the induction of autoimmune responses to self hsp60, since these two proteins share a high degree of amino acid sequence identity. To investigate the conditions under which autoimmune responses can be generated against self hsp60, groups of CBA mice were immunized with recombinant mouse hsp60, recombinant chlamydial hsp60, or both proteins. The data show that autoimmune responses characterized by strong T-cell proliferation and high titers of antibody to self hsp60 are induced only by concurrent immunization with mouse and chlamydial hsp60. Immunization with mouse hsp60 alone induced lymphocytes that secreted high levels of interleukin-10 (IL-10) but did not proliferate in response to in vitro stimulation with mouse hsp60; coimmunization with mouse and chlamydial hsp60s induced lymphocytes that proliferated strongly in response to mouse hsp60, secreted 6-fold less IL-10, and exhibited a 12-fold increase in the ratio of gamma interferon/IL-10 production. Switches in cytokine production patterns may mediate the pathogenesis of hsp60-associated diseases such as C. trachomatis immunopathology.
Yi
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Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Yang
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Brunham
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D000818:Animals; D000906:Antibodies / Q000032:analysis; D000907:Antibodies, Bacterial / Q000032:analysis; D015551:Autoimmunity; D015153:Blotting, Western; D002455:Cell Division; D018834:Chaperonin 60 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D000907:Antibodies, Bacterial; D018834:Chaperonin 60; D007376:Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10; D007371:Interferon-gamma