The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/11/1623/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 10, November 17, 1997 1623-1631


Articles

CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity

Rose S. Chu*, Oleg S. Targoni*, Arthur M. Krieg{ddagger}, Paul V. Lehmann*, and Clifford V. Harding*

From the * Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106; and {ddagger} Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242

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.


Address correspondence to Dr. Clifford V. Harding, Institute of Pathology, Case Western Reserve University, 2085 Adelbert Rd., Cleveland, OH 44106. Phone: (216) 368-4711; FAX: (216) 368-0495; E-mail: cvh3{at}po.cwru.edu

1 Abbreviations used in this paper: HEL, hen egg lysozyme; ODN, oligodeoxynucleotides; PBST, PBS with Tween; S ODN, phosphorothioate-modified ODN; S-O ODN, ODN with partial phosphorothioate modification.

The first two authors contributed equally to this work.


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