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

J Exp Med. 1997 Nov 17;186(10):1623-31. doi: 10.1084/jem.186.10.1623.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / genetics*
  • Animals
  • Antibody Specificity
  • Chickens
  • CpG Islands / immunology*
  • Cytokines / biosynthesis
  • Epitopes / immunology
  • Immunity, Cellular
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin Isotypes / biosynthesis
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Muramidase / immunology
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / immunology
  • Species Specificity
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Thionucleotides / administration & dosage
  • Thionucleotides / immunology


  • Adjuvants, Immunologic
  • Cytokines
  • Epitopes
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Oligodeoxyribonucleotides
  • Thionucleotides
  • Muramidase