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* Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany;
Division of Rheumatology, University of California, Los Angeles, CA 90095;
Department of Nephrology/Transplantation, Charité University Hospital, Humboldt University of Berlin, Berlin, Germany; and
Deutsches Rheumaforschungszentrum, Berlin, Germany
T cells that recognize nucleoproteins are required for the production of anti-dsDNA Abs involved in lupus development. SmD183–119 (a D1 protein of the Smith (Sm) proteins, part of small nuclear ribonucleoprotein) was recently shown to provide T cell help to anti-dsDNA Abs in the NZB/NZW model of lupus. Using this model in the present study, we showed that high dose tolerance to SmD1 (600–1000 µg i.v. of SmD183–119 peptide/mo) delays the production of autoantibodies, postpones the onset of lupus nephritis as confirmed by histology, and prolongs survival. Tolerance to SmD183–119 was adoptively transferred by CD90+ T cells, which also reduce T cell help for autoreactive B cells in vitro. One week after SmD183–119 tolerance induction in prenephritic mice, we detected cytokine changes in cultures of CD90+ T and B220+ B cells with decreased IFN-
and IL-4 expression and an increase in TGF
. Increased frequencies of regulatory IFN-+ and IL10+ CD4+ T cells were later detected. Such regulatory IL-10+/IFN-+ type 1 regulatory T cells prevented autoantibody generation and anti-CD3-induced proliferation of naive T cells. In conclusion, these results indicate that SmD183–119 peptide may play a dominant role in the activation of helper and regulatory T cells that influence autoantibody generation and murine lupus.
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