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- Title
Cellular and Molecular Mechanisms of Regulation of Autoantibody Production in Lupus.
- Authors
HAHN, BEVRA H.; EBLING, FANNY; SINGH, RAM R.; SINGH, RAM P.; KARPOUZAS, GEORGE; CAVA, ANTONIO
- Abstract
The hyperactive interaction between helper T cells and autoimmune B cells in individuals predisposed to systemic lupus erythematosus (SLE) can be interrupted by induction of regulatory and suppressor T cells. Using two strategies—high dose tolerance to an immunoglobulin-derived peptide, and minigene vaccination with DNA encoding T cell epitopes presented by MHC class I molecules—our group has induced at least three types of regulatory/suppressive T cells. They include CD8+ T cells that suppress helper T cells by cytokine secretion, CD8+ T suppressors that kill B cells making anti-DNA antibodies, and peptide-binding CD4+CD25+ regulatory T cells that suppress B cells by direct cell contact. Each of these lymphocyte subsets suppresses anti- DNA antibody production and delays the onset of nephritis in BWF1 lupusprone mice. Patients with SLE have amino acid sequences similar to those from murine anti-DNA antibodies used in these studies, and at similar locations in the VH regions of anti-DNA immunoglobulins. Therefore, strategies described here might ultimately be useful in therapy of the human disease.
- Subjects
AUTOIMMUNE diseases; CELLULAR mechanics; T cells; DNA antibodies; IMMUNOGLOBULINS
- Publication
Annals of the New York Academy of Sciences, 2005, Vol 1051, Issue 1, p433
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1196/annals.1361.085