Cellular and molecular mechanisms of regulation of autoantibody production in lupus.
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 lupus-prone 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.
Hahn
Bevra H
BH
Division of Rheumatology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA 91436, USA. bhahn@mednet.ucla.edu
Ebling
Fanny
F
Singh
Ram R
RR
Singh
Ram P
RP
Karpouzas
George
G
La Cava
Antonio
A
D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies