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CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity.

Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV - J. Exp. Med. (1997)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.

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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CpG ODN decrease HEL-specific IL-5 production by BALB/c splenocytes.  Mice were immunized as in Fig.  2 (30 μg ODN/mouse), and  splenocytes were harvested for in  vitro restimulation with or without HEL. ELISA spot analysis  was performed for IL-5. The  data are representative of five  similar experiments with CpG-  and non–CpG ODN in BALB/c  mice.
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Figure 4: CpG ODN decrease HEL-specific IL-5 production by BALB/c splenocytes. Mice were immunized as in Fig. 2 (30 μg ODN/mouse), and splenocytes were harvested for in vitro restimulation with or without HEL. ELISA spot analysis was performed for IL-5. The data are representative of five similar experiments with CpG- and non–CpG ODN in BALB/c mice.

Mentions: To assess Th2 differentiation, ELISA spot analysis was similarly performed to detect splenocytes producing IL-5 (Fig. 4). Immunization with IFA-HEL induced cells that secreted IL-5 in response to restimulation with HEL, consistent with a Th2-dominated response. In contrast to the results with IFA-HEL, little or no HEL-specific IL-5 secretion was seen in mice immunized with CFA-HEL, consistent with a Th1-dominated anti-HEL response in these mice. HEL-specific IL-5 secretion was observed after immunization with IFA-HEL-non–CpG ODN (e.g., ODN 1745 and ODN 1972), although immunization with IFA-HEL-non–CpG ODN 1745 produced somewhat lower levels of IL-5 than observed with IFA-HEL. In contrast, greater reduction in HEL-specific IL-5 secretion was observed after immunization with CpG ODN (ODN 1826, ODN 1760 and ODN 1585). Thus, the addition of CpG ODN induced a switch from a Th2-dominated response to a Th1-dominated response, as manifested by a decrease in Th2-associated cytokine secretion as well as the induction of Th1-associated cytokine secretion.


CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity.

Chu RS, Targoni OS, Krieg AM, Lehmann PV, Harding CV - J. Exp. Med. (1997)

CpG ODN decrease HEL-specific IL-5 production by BALB/c splenocytes.  Mice were immunized as in Fig.  2 (30 μg ODN/mouse), and  splenocytes were harvested for in  vitro restimulation with or without HEL. ELISA spot analysis  was performed for IL-5. The  data are representative of five  similar experiments with CpG-  and non–CpG ODN in BALB/c  mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199137&req=5

Figure 4: CpG ODN decrease HEL-specific IL-5 production by BALB/c splenocytes. Mice were immunized as in Fig. 2 (30 μg ODN/mouse), and splenocytes were harvested for in vitro restimulation with or without HEL. ELISA spot analysis was performed for IL-5. The data are representative of five similar experiments with CpG- and non–CpG ODN in BALB/c mice.
Mentions: To assess Th2 differentiation, ELISA spot analysis was similarly performed to detect splenocytes producing IL-5 (Fig. 4). Immunization with IFA-HEL induced cells that secreted IL-5 in response to restimulation with HEL, consistent with a Th2-dominated response. In contrast to the results with IFA-HEL, little or no HEL-specific IL-5 secretion was seen in mice immunized with CFA-HEL, consistent with a Th1-dominated anti-HEL response in these mice. HEL-specific IL-5 secretion was observed after immunization with IFA-HEL-non–CpG ODN (e.g., ODN 1745 and ODN 1972), although immunization with IFA-HEL-non–CpG ODN 1745 produced somewhat lower levels of IL-5 than observed with IFA-HEL. In contrast, greater reduction in HEL-specific IL-5 secretion was observed after immunization with CpG ODN (ODN 1826, ODN 1760 and ODN 1585). Thus, the addition of CpG ODN induced a switch from a Th2-dominated response to a Th1-dominated response, as manifested by a decrease in Th2-associated cytokine secretion as well as the induction of Th1-associated cytokine secretion.

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.

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.

Show MeSH
Related in: MedlinePlus