CD8+ T Cell- mediated Suppression of Autoimmunity in a Murine Lupus Model of Peptide-Induced Immune Tolerance Depends on Foxp3 Expression (130.19)

• Published in: The Journal of immunology (1950) Vol. 178; no. 1_Supplement; p. S231
• Main Authors: Singh, Ram P, La Cava, Antonio, Wong, Maida, Tamayo, Alejandro M, Ebling, Fanny M, Hahn, Bevra H
• Format: Journal Article
• Language: English
• Published: 01-04-2007
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.178.Supp.130.19

Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease caused by autoantibodies including IgG anti-DNA. NZB/NZW Fl female (BWF1) mice, a model of spontaneous polygenic SLE, tolerized with an artificial peptide (pCONSENSUS, pCons) based on anti-DNA IgG sequences containing MHC Class I and Class II T cell determinants, develop regulatory CD4+CD25+T cells and inhibitory CD8+T cells (CD8+ Ti), both of which suppress autoAb production. In the present study, using various cellular and molecular approaches, we show that inhibitory function of CD8+ T cells from tolerized mice is sustained for up to 8 weeks and at all times depends on expression of Foxp3. Both CD28− positive and –negative CD8+ T cells contain inhibitory cells, but the expression of Foxp3 and of mRNA for TGFb is higher and lasts longer in the CD28− subset. In vitro addition of TGFb (in the presence of IL-2) induces Foxp3 expression in a dose response manner. Gene inhibition or blockade with siRNA of Foxp3 abrogates the ability of the CD8+ Ti to inhibit anti-DNA production and the proliferation of CD4+ helper T cells. Moreover, we found a significant correlation between expression of Foxp3 and ability of CD8+ Ti cells to secrete TGFb. Therefore, CD8+ Ti in this system of tolerance is depend on expression of Foxp3, and there may be a bi-directional Foxp3/TGFb autocrine loop that determines the ability of the CD8+ T cells to control autoimmunity.
Supported by NIH grants AI63515,AI 63515, AR53239 and Tina C Foundation.