Inhibition of IgE antibody formation by plasmid DNA immunization is mediated by both CD4+ and CD8+ T cells.

Background: We previously showed that immunization of mice with plasmid DNA (pDNA) encoding the Escherichia coli β-galactosidase gene (pCMV-LacZ) induces a Th1 response, whereas β-galactosidase (β-gal) in saline or alum induces a Th2 response. Furthermore, the Th1 response 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 β2-microglobulin knockout (β2-M KO) mice whether CD4+ and /or CD8+ cells from pDNA-immunized mice suppress IgE antibody production. Methods: BALB/c mice were injected with either CD4+ or CD8+ lymphocytes from naive β-gal-in-alum or pCMV-LacZ-immunized mice, then immunized with β-gal in alum, and the IgE antibody formation was determined. Second, C57BL/6 wild-type (WT) or β2-M KO mice were immunized with β-gal or pCM V-LacZ, and the 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 from naive or β-gal-in-alum immunized mice. β2-M KO mice produced 3 times more IgE than the WT control mice both in the primary and secondary response. Conclusion: Both CD4+ and CD8+ subsets of T cells from pDNA-immunized mice can suppress IgE antibody production by affecting the primary response and/or by propagating the Thl memory response in a passive cell transfer system. Immunization with pDNA-encoding allergens may be an effective new form of immunotherapy for atopic diseases.