Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization - PubMed (original) (raw)

Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization

E Raz et al. Proc Natl Acad Sci U S A. 1996.

Abstract

We compared the antigen-specific antibody isotypes and lymphokine secretion by CD4+ T cells in BALB/c mice immunized intradermally with either Escherichia coli beta-galactosidase (beta-gal) or plasmid DNA (pDNA) encoding beta-gal in a cytomegalovirus-based expression vector (pCMV-LacZ). pCMV-LacZ induced mainly IgG2a, whereas beta-gal in saline or 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 interferon-gamma after in vitro stimulation with antigen. Together these data demonstrate that pDNA immunization induced a T helper type 1 (Th1) response, whereas protein immunization induced a T helper type 2 (Th2) response to the same antigen. Interestingly, priming of mice with pCMV-LacZ prevented IgE antibody formation to a subsequent i.p. beta-gal in alum injection. This effect was antigen-specific, because priming with pCMV-LacZ did not inhibit IgE anti-ovalbumin antibody formation. Most importantly, intradermal immunization with pCMV-LacZ (but not 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 specific IgG2a antibody titers and interferon-gamma secretion by Th cells in the beta-gal in alum-primed mice. The data demonstrate that gene immunization induces a Th1 response that dominates over an ongoing protein-induced Th2 response in an antigen-specific manner. This suggests that immunization with pDNA encoding for allergens may provide a novel type of immunotherapy for allergic diseases.

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References

1. 1. Annu Rev Immunol. 1985;3:237-61 - PubMed
2. 1. J Immunol. 1995 Jul 1;155(1):259-65 - PubMed
3. 1. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9675-8 - PubMed
4. 1. J Immunol. 1987 Sep 1;139(5):1459-65 - PubMed
5. 1. Eur J Immunol. 1988 Jul;18(7):1045-50 - PubMed

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