PREFERENTIAL INDUCTION OF A TH-1 IMMUNE-RESPONSE AND INHIBITION OF SPECIFIC IGE ANTIBODY-FORMATION BY PLASMID DNA IMMUNIZATION

We compared the antigen-specific antibody isotypes and lymphokine secr etion by CD4(+) T cells in BALB/c mice immunized intradermally with ei ther Escherichia coli beta-galactosidase (beta-gal) or plasmid DNA (pD NA) encoding beta-gal in a cytomegalovirus-based expression vector (pC MV-LacZ). pCMV-LacZ induced mainly IgG2a, whereas beta-gal in saline o r alum induced IgG1 and IgE beta-gal-specific antibodies. In addition, splenic CD4(+) T helper (Th) cells isolated from pDNA-immunized mice secreted interferon-gamma but not interleukin (IL)-4 and IL-5, whereas Th cells from beta-gal-injected mice secreted IL-4 and IL-5 but not i nterferon-gamma after in vitro stimulation with antigen. Together thes e data demonstrate that pDNA immunization induced a T helper type 1 (T h-1) response, whereas protein immunization induced a T helper type 2 (Th-2) response to the same antigen. Interestingly, priming of mice wi th pCMV-LacZ prevented IgE antibody formation to a subsequent i.p. bet a-gal in alum injection. This effect was antigen-specific, because pri ming with pCMV-LacZ did not inhibit IgE anti-ovalbumin antibody format ion. Most importantly, intradermal immunization with pCMV-LacZ (but no t pCMV-OVA) of beta-gal in alum-primed mice caused a 66-75% reduction of the IgE anti-beta-gal titer in 6 weeks. Also, pCMV-LacZ induced spe cific IgG2a antibody titers and interferon-gamma secretion by Th cells in the beta-gal in alum-primed mice. The data demonstrate that gene i mmunization induces a Th-1 response that dominates over an ongoing pro tein-induced Th-2 response in an antigen-specific manner. This suggest s that immunization with pDNA encoding for allergens may provide a nov el type of immunotherapy for allergic diseases.