INHIBITION OF IGE ANTIBODY-FORMATION BY PLASMID DNA IMMUNIZATION IS MEDIATED BY BOTH CD4-CELLS( AND CD8+ T)

Background: We previously showed that immunization of mice with plasmi d DNA (pDNA) encoding the Escherichia coli beta-galactosidase gene (pC MV-LacZ) induces a Th1 response, whereas beta-galactosidase (beta-gal) in saline or alum induces a Th2 response. Furthermore, the Th1 respon se dominates over the Th2 response and downregulates preexisiting IgE antibody formation. Here, we determined by passive transfer of CD4+ or CD8+ lymphocytes and by immunizing beta(2)-microglobulin knockout (be ta(2)-M KO) mice whether CD4+ and/or CD8+ cells from pDNA-immunized mi ce suppress IgE antibody production. Methods: BALB/c mice were injecte d with either CD4+ or CD8+ lymphocytes from naive beta-gal-in-alum or pCMV-LacZ-immunized mice, then immunized with beta-gal in alum, and th e IgE antibody formation was determined. Second, C57BL/6 wildtype (WT) or beta(2)-M KO mice were immunized with beta-gal or pCMV-LacZ, and t he IgE antibody production was assessed. Results: Passive transfer of both CD4+ and CD8+ lymphocytes from pDNA-immunized mice suppressed the IgE antibody response by 90% compared to transfer of CD4+ T cells fro m naive or beta-gal in-alum immunized mice. beta(2)-M KO mice produced 3 times more IgE than the WT control mice both in the primary and sec ondary response. Conclusion: Both CD4+ and CD8+ subsets of T cells fro m pDNA-immunized mice can suppress IgE antibody production by affectin g the primary response and/or by propagating the Th1 memory response i n a passive cell transfer system. Immunization with pDNA-encoding alle rgens may be an effective new form of immunotherapy for atopic disease s.