Inhibition of IgE Antibody Formation by Plasmid DNA Immunization Is Mediated by both CD4+ and CD8+ T Cells

Abstract

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.

DNA immunization: a novel approach to allergen‐specific immunotherapy

“…Tliis indicates that the pDNA immunization induced both IFN-yproducing antigen-specific CD4+ and CDB-i-cells, and that the transferred cells inhibited the IgE formation either by affecting the primary response, by propagating the Thl response of the transferred cells, or by both actions. Moreover, when Pjmicroglobulin knockout mice, which have few functional CD84-T cells, were immunized with Pgal in alum, they produced threefold more IgE antibodies than the wild-type C57BL control mice (20). pCMV-lacZ did not induce IgE antibodies in both types of mice.…”

“…Lee et al (20) passively transferred CD4+ or CDB-i-splenic T cells to naive mice and immunized them 2 days later with P-gal in alum. Passive transfer of CD4-I-or CD8-I-T cells from pCMV-/flcZ-immunized mice suppressed the IgE antibody formation by 90% as compared to the transfer of T cells from naive or p-gal in alum-immunized mice.…”

CD8 T Cells Inhibit IgE Via Dendritic Cell IL-12 Induction That Promotes Th1 T Cell Counter-Regulation

“…Indeed, CD8 T cells primed in vivo with low affinity peptides could kill efficiently in vitro (42). Strategies for facilitating such presentation of Ag to TCR, for example as an approach to treating allergies, could include DNA immunization (43,44) and cationic lipid encapsulation of antigenic peptide that directly fuses with the APC cell membrane, thus introducing Ag into the cytosol and therefore the MHC class I processing pathway. Crosspriming in which soluble Ag enters the MHC class I pathway has been well established by a number of investigators (15,(45)(46)(47).…”

Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

“…8,14 Induction of CD8 + T cells, as well as a shift towards a Th1 immune response contributed to this effect. 7,8,13,14,19,20 However, successful curative allergen gene transfer for the suppression of already established IgE Ab immune responses was reported only by three groups, 7,14,15 rendering it likely to improve therapeutic DNA vaccination by gene transfer with more efficient vehicles.…”