CD8 super(+) T Cell-Mediated Suppression of Autoimmunity in a Murine Lupus Model of Peptide-Induced Immune Tolerance Depends on Foxp3 Expression

Systemic lupus erythematosus is an autoimmune disease caused by autoantibodies, including IgG anti-DNA. New Zealand Black/New Zealand White F sub(1) female mice, a model of spontaneous polygenic systemic lupus erythematosus, tolerized with an artificial peptide (pConsensus) based on anti-DNA IgG seq...

Full description

Saved in:
Bibliographic Details
Published in:Journal of Immunology 2007-06, Vol.178 (12), p.7649-7657
Main Authors: Singh, Ram Pyare, La Cava, Antonio, Wong, Maida, Ebling, Fanny, Hahn, Bevra H
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Systemic lupus erythematosus is an autoimmune disease caused by autoantibodies, including IgG anti-DNA. New Zealand Black/New Zealand White F sub(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 super(+)CD25 super(+) T cells and CD8 super(+) inhibitory T cells (CD8 super(+) Ti), both of which suppress autoantibody production. CD8 super(+) Ti inhibit primarily via secretion of TGF- beta . In the present study, we show that the inhibitory function of CD8 super(+) 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 super(+) T cells contain inhibitory cells, but the expression of mRNA for Foxp3 and for TGF- beta is higher and lasts longer in the CD28 super(-) 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 super(+) Ti to inhibit anti-DNA production and the proliferation of CD4 super(+) Th cells. Moreover, a significant correlation between expression of Foxp3 and ability of CD8 super(+) Ti to secrete TGF- beta is observed. Therefore, CD8 super(+) Ti in this system of tolerance are similar to CD4 super(+)CD25 super(+) 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 super(+) T cells to control autoimmunity.
ISSN:0022-1767
1365-2567