Role of IFI202b in the suppressive ability of CD8+Treg induced in (NZB x NZW) F1 lupus mice (143.56)

Abstract

Abstract Tolerance with an artificial peptide (pConsensus, pCons) based on anti-DNA IgG sequences containing MHC class I and class II T cell determinants, causes NZB/NZW F1 female (BWF1) mice to develop CD8+Foxp3+ inhibitory T (Ti) cells which suppress anti-DNA Ig production. CD8+T cells from mice tolerized with pCons expressed Ifi202b more than two-fold higher than cells from untolerized mice, with an increase 1-4 weeks after tolerization and a return toward baseline at 6 weeks. In vitro polyclonal activation significantly increased Ifi202b mRNA expression in tolerized CD8+T cells. Importantly, silencing of Ifi202b abrogated the suppressive capacity of tolerized CD8+T cells. This was associated with decreased expression of Foxp3, and decreased gene and protein expression of TGFb, but not of IL-2, IFN-g, IL-10 or IL-17. These changes were not related with resistance to apoptosis induced in CD8+Treg. Although Ifi202b is induced by interferons, silencing of another IFN-induced gene upregulated in tolerized CD8+T cells, IFNar1, had no effect on the ability of CD8+T cells to suppress autoantibody production. Taken together, these data identify a role for Ifi202b in the suppressive capacity of peptide-induced regulatory CD8+T cells via effects on the expression of Foxp3 and the synthesis of TGFb.