CpG Oligodeoxynucleotides Act As Adjuvants That Switch on T Helper 1 (Th1) Immunity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1997 Dec 31

PMID 9362523

Citations 254

Authors

R S Chu

O S Targoni

A M Krieg

P V Lehmann

C V Harding

Affiliations

Soon will be listed here.

Abstract

Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-gamma secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-gamma. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-gamma secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non-CpG ODN did not induce IFN-gamma or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.

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References

Forsthuber T, Yip H, Lehmann P . Induction of TH1 and TH2 immunity in neonatal mice. Science. 1996; 271(5256):1728-30. DOI: 10.1126/science.271.5256.1728. View

Bliss J, Van Cleave V, Murray K, Wiencis A, Ketchum M, Maylor R . IL-12, as an adjuvant, promotes a T helper 1 cell, but does not suppress a T helper 2 cell recall response. J Immunol. 1996; 156(3):887-94. View

Raz E, Tighe H, Sato Y, Corr M, Dudler J, Roman M . Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc Natl Acad Sci U S A. 1996; 93(10):5141-5. PMC: 39421. DOI: 10.1073/pnas.93.10.5141. View

COWDERY J, Chace J, Yi A, Krieg A . Bacterial DNA induces NK cells to produce IFN-gamma in vivo and increases the toxicity of lipopolysaccharides. J Immunol. 1996; 156(12):4570-5. View

Sato Y, Roman M, Tighe H, Lee D, Corr M, Nguyen M . Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science. 1996; 273(5273):352-4. DOI: 10.1126/science.273.5273.352. View

Ballas Z, Rasmussen W, Krieg A . Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J Immunol. 1996; 157(5):1840-5. View

Stacey K, Sweet M, Hume D . Macrophages ingest and are activated by bacterial DNA. J Immunol. 1996; 157(5):2116-22. View

Krieg A . Lymphocyte activation by CpG dinucleotide motifs in prokaryotic DNA. Trends Microbiol. 1996; 4(2):73-6. DOI: 10.1016/0966-842X(96)81515-0. View

Pisetsky D . Immune activation by bacterial DNA: a new genetic code. Immunity. 1996; 5(4):303-10. DOI: 10.1016/s1074-7613(00)80256-3. View

10.

Abbas A, Murphy K, Sher A . Functional diversity of helper T lymphocytes. Nature. 1996; 383(6603):787-93. DOI: 10.1038/383787a0. View

11.

Sparwasser T, Miethke T, Lipford G, Borschert K, Hacker H, Heeg K . Bacterial DNA causes septic shock. Nature. 1997; 386(6623):336-7. DOI: 10.1038/386336a0. View

12.

Monteith D, Henry S, Howard R, Flournoy S, Levin A, Bennett C . Immune stimulation--a class effect of phosphorothioate oligodeoxynucleotides in rodents. Anticancer Drug Des. 1997; 12(5):421-32. View

13.

Chace J, Hooker N, Mildenstein K, Krieg A, COWDERY J . Bacterial DNA-induced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12. Clin Immunol Immunopathol. 1997; 84(2):185-93. DOI: 10.1006/clin.1997.4380. View

14.

Bird A . CpG-rich islands and the function of DNA methylation. Nature. 1986; 321(6067):209-13. DOI: 10.1038/321209a0. View

15.

Stein C, Subasinghe C, Shinozuka K, Cohen J . Physicochemical properties of phosphorothioate oligodeoxynucleotides. Nucleic Acids Res. 1988; 16(8):3209-21. PMC: 336489. DOI: 10.1093/nar/16.8.3209. View

16.

Scott P, Natovitz P, Coffman R, Pearce E, Sher A . Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988; 168(5):1675-84. PMC: 2189120. DOI: 10.1084/jem.168.5.1675. View

17.

Heinzel F, Sadick M, Holaday B, Coffman R, Locksley R . Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989; 169(1):59-72. PMC: 2189187. DOI: 10.1084/jem.169.1.59. View

18.

Mosmann T, Coffman R . TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989; 7:145-73. DOI: 10.1146/annurev.iy.07.040189.001045. View

19.

Sadick M, Heinzel F, Holaday B, Pu R, Dawkins R, Locksley R . Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism. J Exp Med. 1990; 171(1):115-27. PMC: 2187647. DOI: 10.1084/jem.171.1.115. View

20.

Finkelman F, Holmes J, Katona I, Urban Jr J, Beckmann M, Park L . Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol. 1990; 8:303-33. DOI: 10.1146/annurev.iy.08.040190.001511. View