Cd8+ T Cell-mediated Suppression of Autoimmunity in a Murine Lupus Model of Peptide-induced Immune Tolerance Depends on Foxp3 Expression.
From: Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, 1001 Veteran Avenue, Los Angeles, CA 90095, USA.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jun 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 12
- Pages: 7649-57
- Medium: Print
- Language: English
- Citation (JAMA): Singh Ram Pyare, La Cava Antonio, Wong Maida, et al. Cd8+ T Cell-mediated Suppression of Autoimmunity in a Murine Lupus Model of Peptide-induced Immune Tolerance Depends on Foxp3 Expression.. J. Immunol. Jun 2007;178:7649-57
Abstract
Systemic lupus erythematosus is an autoimmune disease caused by autoantibodies, including IgG anti-DNA. New Zealand Black/New Zealand White F(1) female mice, a model of spontaneous polygenic systemic lupus erythematosus, tolerized with an artificial peptide (pConsensus) based on anti-DNA IgG sequences containing MHC class I and class II T cell determinants, develop regulatory CD4+CD25+ T cells and CD8+ inhibitory T cells (CD8+ Ti), both of which suppress autoantibody production. CD8+ Ti inhibit primarily via secretion of TGF-beta. In the present study, we show that the inhibitory function of CD8+ T cells from tolerized mice is sustained for up to 8 wk and at all times depends on expression of Foxp3. Both CD28-positive and CD28-negative CD8+ T cells contain inhibitory cells, but the expression of mRNA for Foxp3 and for TGF-beta is higher and lasts longer in the CD28- subset. In vitro addition of TGF-beta (in the presence of IL-2) induces Foxp3 expression in a dose-response manner. Gene inhibition or blockade with small interfering RNA of Foxp3 abrogates the ability of the CD8+ Ti to inhibit anti-DNA production and the proliferation of CD4+ Th cells. Moreover, a significant correlation between expression of Foxp3 and ability of CD8+ Ti to secrete TGF-beta is observed. Therefore, CD8+ Ti in this system of tolerance are similar to CD4+CD25+ regulatory T cells in their dependence on expression of Foxp3, and there may be a bidirectional Foxp3/TGF-beta autocrine loop that determines the ability of the CD8+ T cells to control autoimmunity.
Mesh Headings (Keywords): Animals, Antibodies, Antinuclear, Autoimmunity, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Disease Models, Animal, Female, Forkhead Transcription Factors, Immune Tolerance, Immunoglobulin G, Lupus Erythematosus, Systemic, Mice, Mice, Inbred Strains, Peptides, RNA, Messenger, T-Lymphocytes, Helper-Inducer, Transforming Growth Factor beta
Check for Full Text / PubMed Unique Identifier (PMID): 17548601
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