Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self.
J Immunol
; 162(11): 6482-91, 1999 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-10352263
ABSTRACT
One of the hallmarks of systemic autoimmune diseases is immune responses to systemic nuclear autoantigens. We have examined the fate of the immune response against a nuclear autoantigen using human U1 small nuclear ribonucleoprotein-A protein (HuA) transgenic (Tg) mice by adoptive transfer of autoreactive lymphocytes. We obtained two Tg lines that have different expression levels of the transgene. After spleen cells from HuA-immunized wild-type mice were transferred to Tg mice and their non-Tg littermates, these recipients were injected with HuA/IFA to induce a recall memory response. HAB69, which expressed a lower amount of HuA, exhibited a vigorous increase in the autoantibody level and glomerulonephritis. Moreover, the autoreactivity spread to 70K autoantigen. Alternatively, in HAB64, which expressed a higher amount of HuA, the production of autoantibody was markedly suppressed. The immune response to HuA autoantigen was impaired as demonstrated in a both delayed-type hypersensitivity response and proliferation assay. This inhibition was Ag-specific and was mediated by T cells. These data suggest that the expression level of systemic autoantigens influences the outcome of the immune response to self.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autoantibodies
/
Autoantigens
/
Cell Nucleus
/
RNA-Binding Proteins
/
Ribonucleoprotein, U1 Small Nuclear
Type of study:
Etiology_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Immunol
Year:
1999
Document type:
Article
Affiliation country:
Japan