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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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Induction of HEL-specific IFN-γ responses by CpG  ODN in B10.D2 mice. B10.D2  mice were immunized as in Fig.  1, except that ODN were used  at 30 μg per mouse. Three  weeks after immunization, HEL-specific production of IFN-γ by  splenocytes was measured by  ELISA spot assay as in Fig. 2.  The data shown are representative of three similar experiments.
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Figure 5: Induction of HEL-specific IFN-γ responses by CpG ODN in B10.D2 mice. B10.D2 mice were immunized as in Fig. 1, except that ODN were used at 30 μg per mouse. Three weeks after immunization, HEL-specific production of IFN-γ by splenocytes was measured by ELISA spot assay as in Fig. 2. The data shown are representative of three similar experiments.

Mentions: Strains of mice differ in genetic bias toward the development of Th1- or Th2-dominated Th responses. Earlier publications have demonstrated that BALB/c mice are Th2-biased, while B10.D2 mice are more Th1-biased (20). To explore the impact of varying Th1/Th2 bias on the effect of CpG ODN, B10.D2 mice were injected i.p. with IFA-HEL, with or without 30 μg CpG ODN 1826 or non–CpG ODN 1745, and splenocytes were subsequently isolated for ELISA spot analysis. Immunization with IFA-HEL-CpG ODN 1826 produced a very high level of HEL-specific IFN-γ production, while IFN-γ was not produced after immunization with IFA-HEL alone (Fig. 5). Again, CpG ODN 1826 induced levels of HEL-specific IFN-γ production that exceeded even those seen after immunization with CFA-HEL, and augmentation of IFN-γ production, albeit at lower levels, was seen in B10.D2 mice treated with as little as 3 μg of ODN 1826 in IFA-HEL (data not shown). Immunization with IFA-HEL plus either of the two other CpG ODN, ODN 1760, and ODN 1585, also induced HEL-specific secretion of IFN-γ (data not shown). Immunization with the non–CpG ODN 1745 and 1908 (30 μg dose) induced HEL-specific production of IFN-γ by splenocytes from B10.D2 mice, but at a minimal level (Fig. 5 and data not shown), while the other non–CpG ODN, ODN 1972, did not induce IFN-γ (data not shown). Thus, CpG ODN had strong Th1 adjuvant activity in Th1-biased as well as Th2-biased mice, while non–CpG ODN induced little or no Th1 differentiation, as assessed by antigen-specific secretion of IFN-γ.


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)

Induction of HEL-specific IFN-γ responses by CpG  ODN in B10.D2 mice. B10.D2  mice were immunized as in Fig.  1, except that ODN were used  at 30 μg per mouse. Three  weeks after immunization, HEL-specific production of IFN-γ by  splenocytes was measured by  ELISA spot assay as in Fig. 2.  The data shown are representative of three similar experiments.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2199137&req=5

Figure 5: Induction of HEL-specific IFN-γ responses by CpG ODN in B10.D2 mice. B10.D2 mice were immunized as in Fig. 1, except that ODN were used at 30 μg per mouse. Three weeks after immunization, HEL-specific production of IFN-γ by splenocytes was measured by ELISA spot assay as in Fig. 2. The data shown are representative of three similar experiments.
Mentions: Strains of mice differ in genetic bias toward the development of Th1- or Th2-dominated Th responses. Earlier publications have demonstrated that BALB/c mice are Th2-biased, while B10.D2 mice are more Th1-biased (20). To explore the impact of varying Th1/Th2 bias on the effect of CpG ODN, B10.D2 mice were injected i.p. with IFA-HEL, with or without 30 μg CpG ODN 1826 or non–CpG ODN 1745, and splenocytes were subsequently isolated for ELISA spot analysis. Immunization with IFA-HEL-CpG ODN 1826 produced a very high level of HEL-specific IFN-γ production, while IFN-γ was not produced after immunization with IFA-HEL alone (Fig. 5). Again, CpG ODN 1826 induced levels of HEL-specific IFN-γ production that exceeded even those seen after immunization with CFA-HEL, and augmentation of IFN-γ production, albeit at lower levels, was seen in B10.D2 mice treated with as little as 3 μg of ODN 1826 in IFA-HEL (data not shown). Immunization with IFA-HEL plus either of the two other CpG ODN, ODN 1760, and ODN 1585, also induced HEL-specific secretion of IFN-γ (data not shown). Immunization with the non–CpG ODN 1745 and 1908 (30 μg dose) induced HEL-specific production of IFN-γ by splenocytes from B10.D2 mice, but at a minimal level (Fig. 5 and data not shown), while the other non–CpG ODN, ODN 1972, did not induce IFN-γ (data not shown). Thus, CpG ODN had strong Th1 adjuvant activity in Th1-biased as well as Th2-biased mice, while non–CpG ODN induced little or no Th1 differentiation, as assessed by antigen-specific secretion of IFN-γ.

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