Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

Type 1 regulatory T cells in treatment of murine lupus

  • R Undeutsch1,
  • J Humrich1,
  • BH Hahn2,
  • F Hiepe1,
  • G Burmester1,
  • A Radbruch3 and
  • G Riemekasten1
Arthritis Research & Therapy20057(Suppl 1):P95

DOI: 10.1186/ar1616

Received: 11 January 2005

Published: 17 February 2005

Systemic lupus erythematosus is a severe systemic autoimmune disease characterized by loss of tolerance towards a restricted panel of autoantigens. As a result, pathogenic autoantibodies against dsDNA or the Sm proteins occur. We identified the SmD1(83-119) peptide, the C-terminus of the spliceosomal protein SmD1, as a major B-cell and T-cell autoantigen in human and murine lupus [13]. In previous work we could show that intravenous high-dose application of SmD1(83-119) prolongs survival in NZB/W F1 mice and delays occurrence of anti-dsDNA autoantibodies [4]. Higher percentages of CD4+ T cells that produce IL-10 and interferon gamma were detected on restimulation with phorbol 12-myristate 13-acetate/ionomycin later on in the spleen, indicating involvement of type 1 regulatory T cell (Tr1 cell)-mediated tolerance [4]. Transfer of splenic CD90+ T cells from mice treated with high doses of SmD1(83-119) into untreated mice delayed the occurrence of anti-dsDNA autoantibodies in these recipients as well [4].

We now performed a SmD1(83-119) specific analysis of the CD4+ T cells after high-dose application of SmD1(83-119) and detected SmD1(83-119)-reactive CD4+IL-10+ Tr1 cells in the spleen and in draining lymph nodes after additional immunization with SmD1(83-119). In vitro experiments showed that Tr1-cell-mediated suppression of anti-DNA autoantibody production is dependent on the activity of IL-10 as the addition of neutralizing anti-IL-10 antibodies abrogated this effect. Furthermore, adoptive transfer of SmD1(83-119) reactive Tr1-cell-containing lymph node cells delayed the occurrence of anti-DNA autoantibodies in the recipient mice as well.

We conclude that high-dose application of SmD1(83-119) induces SmD1(83-119) specific tolerance in NZB/W F1 mice, which is mediated by SmD1(83-119)-reactive Tr1 cells. These results may open new ways for future autoantigen specific cell-based therapies in systemic lupus erythematosus.



RU and JH contributed equally to this work.

Authors’ Affiliations

Charité University Hospital
University of California
German Arthritis Research Centre


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© BioMed Central Ltd 2005