pConsensus peptide induces tolerogenic CD8+T cells in lupus‐prone (NZB x NZW) F1 mice by differentially regulating Foxp3 and PD1 molecules

Systemic lupus erythematosus (SLE) is an autoimmune disease caused primarily by autoantibodies (including IgG anti‐DNA) and immune complexes. Tolerization with an artificial peptide (pCONSENSUS, pCons) based on murine anti‐DNA IgG sequences containing MHC class I and class II T cell determinants, lupus‐prone NZB/NZW F1 female (BWF1) mice develop regulatory CD4+CD25+T cells and inhibitory CD8+T cells, both of which suppress anti‐DNA Ig production and immune glomerulonephritis. In the present work, we show that splenocytes from BWF1 mice treated with pCons had significant expansion of primarily CD8+T cells. CD4+ T cells and B cells were each directly suppressed by CD8+T cells from tolerized mice in a contact‐independent manner. Both pCons‐ induced CD8+CD28+ and CD8+CD28− T cells suppressed production of anti‐DNA in vitro. Silencing with siRNA of Foxp3 abrogated the suppression mediated by both CD8+ T cell subsets. In addition, CD8+ T cells from tolerized mice were weakly cytotoxic against syngeneic B cells from old anti‐DNA‐producing mice, but not from young mice. Importantly, CD8+ suppressor T cells from tolerized mice, increases the intracellular expression of Foxp3 while decreases the surface expression of PD1 molecules. Blocking PD1/PDL1 interactions in the CD8+ T cells from tolerized mice reduced their expression of Foxp3 and their ability to suppress CD4+CD25− proliferation.