Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Production of autoantibodies by B cells in systemic lupus erythematosus (SLE) can be interrupted via induction of regulatory and suppressor T cells. We have used the strategy of tolerizing lupus-prone (NZBxNZW)F(1) mice with an artificial peptide based on sequences common to several anti-double stranded (ds)DNA antibodies to induce regulatory and suppressor T cells that block production of anti-DNA antibodies and prolong their survival. At least one type of suppressor T cells (CD8+) and one type of regulatory T cell (CD4+ expressing the IL-2 receptor alpha chain CD25) are raised under this condition. While CD8+ suppressors (TS) require soluble factors to block help of T cells to B cells, regulatory CD4+CD25+ T cells (TR) curb the production of anti-DNA antibodies from B cells via cell contact through molecules that include membrane-bound TGFbeta and GITR. Moreover, CD8+ suppressors seem to act independently on antigen specificity, while TR act in an antigen-specific fashion. We hypothesize that the differences between these two lymphocyte subsets that share the common ability to dampen production of autoantibodies might underlie significant temporal and teleological advantages for optimal control of autoimmune reactivity.
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PMID:Manipulation of immune regulation in systemic lupus erythematosus. 1621 88

GITR (glucocorticoid-induced TNF receptor) is a recently identified member of the TNF receptor superfamily. The receptor is preferentially expressed on CD4+CD25+ regulatory T cells and GITR signals break the suppressive activity of the subset. In this study, we wanted to reveal the in vivo function of GITR in chronic graft-versus-host disease (cGVHD), a lupus-like autoimmune disease. A single injection of anti-GITR monoclonal antibody (DTA-1) was effective in blocking the progression of cGVHD in the parent-into-F1 model. Treatment of DTA-1 significantly decreased levels of IgG1 anti-DNA autoantibody, inhibited glomerulonephritis, and increased survival. The DTA-1-mediated inhibition of autoantibody production correlated with deletion of B cells and could occur independently of CD4+CD25+ regulatory T cells. Our results indicate that anti-GITR monoclonal antibody may be used as a potential immunotherapeutic agent for preventing cGVHD.
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PMID:Prevention of chronic graft-versus-host disease by stimulation with glucocorticoid-induced TNF receptor. 1652 May 57

B cell depletion may affect T cell activation and costimulation status in rituximab-treated patients with SLE. We examined whether rituximab administration in patients with active lupus nephritis is related to changes in mRNA expression of genes that define regulatory T cells (Tregs) in peripheral blood lymphocytes, measured by real-time PCR. At the early phase of B cell depletion mRNA levels of CD25, CTLA-4, GITR and the bona fide Treg functional marker FOXP3 increased significantly in all 7 patients examined. In contrast, mRNA levels of the costimulatory/activation T cell molecule CD40L were profoundly reduced, while mRNA levels of TGF-beta, a cytokine contributing to Treg induction, increased significantly in all. During follow-up, increased FOXP3 mRNA persisted in those patients in clinical remission, while in those patients with active disease subsequent decreases were noted. Further studies should examine whether modulation of Tregs by therapeutic B cell depletion contributes and/or predicts lupus disease remission.
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PMID:Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. 1727 13

The bi-annual FASEB autoimmunity conference organized last year by Betty Diamond and Stephen Miller brought together some 150 delegates studying various aspects of autoimmune diseases such as lupus, rheumatoid arthritis and autoimmune diabetes. The conference provided numerous insights into the latest research on autoimmunity and answered many basic research type questions that are important for understanding the complex nature of these diseases. Because some time has elapsed since the conference, data from a number of talks has already been published. Thus, I will present an overview of some of the most interesting and at the same time, still unpublished data on T cells presented at the conference. The balance between tolerance and immunity is controlled through a variety of mechanisms such as the presence or absence of co-stimulation or negative regulation of a T cell response. CD4+ CD25+ regulatory T cells were also a focus of interest. Talks that I will discuss focused on the role of molecules such as GITR, Foxp3 and B7 for the development and function of regulatory T cells and the importance of these molecules in the prevention of autoimmunity. As well, a novel form of CTLA-4 and the use of 4-1BB co-stimulation blockade for the control of autoimmunity will be discussed.
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PMID:Novel insights in the regulation of the immune system: a report on the FASEB summer research conference on autoimmunity (June 14-19, 2003, Saxton's River, Vermont, USA). 1749 65