Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells

Gabriela Riemekasten*, Dirk Langnickel, Philipp Enghard, Reinmar Undeutsch, Jens Humrich, Fanny M. Ebling, Berthold Hocher, Tiina Humaljoki, Hans Neumayer, Gerd R. Burmester, Bevra H. Hahn, Andreas Radbruch, Falk Hiepe

*Corresponding author for this work
34 Citations (Scopus)


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 SmD183-119peptide/mo) delays the production of autoantibodies, postpones the onset of lupus nephritis as confirmed by histology, and prolongs survival. Tolerance to SmD1 83-119 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 B22O+ B cells with decreased IFN-γ and IL-4 expression and an increase in TGFβ. Increased frequencies of regulatory IFN-γ+ and IL10+ CD4+ T cells were later detected. Such regulatory IL-10 +/IFN-γ+ 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.

Original languageEnglish
JournalJournal of Immunology
Issue number9
Pages (from-to)5835-5842
Number of pages8
Publication statusPublished - 01.11.2004

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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