Transduced B‐cells mediate tolerance by activating regulatory T‐cells

Abstract

FoxP3 has emerged as an intracellular marker for mouse T cells that have a regulatory phenotype. To study the kinetics of regulatory T cell induction in response to treatment from tolerogenic B cells, we have crossed the FoxP3‐GFP knock‐in mouse to our mouse model for hemophilia; we have also crossed the FoxP3‐GFP mouse to a transgenic mouse with an ovalbumin specific TCR. We use the established gene‐therapy technique of transducing LPS activated B cells with an antigen‐IgG fusion to prevent or abrogate an ongoing immune response. Although it has already been shown that tolerance is dependent on CD4+CD25+ regulatory cells, herein, we demonstrate an increase in levels of antigen specific FoxP3+ cells that peaks within a week of treatment and wanes near baseline levels by two weeks. Additionally, we see an increased response of regulatory cells following challenge with antigen. We anticipate that a deeper understanding of the kinetics of FoxP3 induction will likely lead to insight into treatment modalities to maintain high levels of regulatory cells during the management of autoimmune diseases, transplant, and protein based therapies.(Supported by NIH grants R01 HL061883 and T32 HL07698)