Antigen-specific induction of peripheral T cell tolerance in vivo by codelivery of DNA vectors encoding antigen and Fas ligand

Fas ligand (FasL, CD95L) induces apoptosis in activated T cells with upregulated Fas (CD95) expression through the process termed activation-induced cell death (AICD), We postulated that coexpression of antigen and Fast within individual antigen-presenting cells would lead to antigen-specific activation of T cells and to their consequent deletion by Fast-mediated AICD, A DNA-gelatin coacervate containing transferrin cell ligand, calcium, and the lysosomatropic agent chloroquine, a formulation previously shown to achieve high-level transfection of immune and muscle cells in vivo, was used to codeliver plasmids encoding Fast and antigen, Mice developed a strong cytolytic T cell response to beta-Gal when injected with DNA encoding beta-galactosidase (LacZ) model antigen, either as naked DNA or DNA nanoparticles, but failed to respond when there was concomitant injection of nanoparticles containing both the LacZ and murine Fast DNA vectors, This loss of T cell response was systemic, specific for beta-Gal, complete when nonoparticles were administered before antigen challenge, and decreased the T cell response: from prior immunization with LacZ DNA, In effect, this "tolerization" injection induced antigen-specific peripheral tolerance in study mice, and represents a possible approach to the treatment of autoimmuue diseases and transplantation rejection.