CpG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo.
The mechanism of action of microbial adjuvants in promoting the differentiation of autoimmune effector cells remains to be elucidated. We demonstrate that CpG-containing oligodeoxynucleotides (ODN) can completely substitute for heat-killed mycobacteria in the priming of encephalitogenic myelin-reactive T cells in vivo. The adjuvanticity of the CpG ODN was secondary to their direct ability to induce IL-12 or to act synergistically with endogenous IL-12 to promote Th1 differentiation and encephalitogenicity. T cells primed in the absence of CpG with Ag and IFA alone appeared to be in a transitional state and had not undergone differentiation along a conventional Th pathway. Unlike Th2 cells, they expressed low levels of the IL-12R beta 2 subunit and retained the ability to differentiate into encephalitogenic effectors when reactivated in vitro under Th1-polarizing conditions. These results support the use of CpG ODN as adjuvants but also suggest that they could potentially trigger autoimmune disease in a susceptible individual.
Segal
B M
BM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Chang
J T
JT
Shevach
E M
EM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000502:physiology; D008055:Lipids; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides / Q000008:administration & dosage / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D001324:Autoantigens; C408982:CPG-oligonucleotide; D008055:Lipids; D004676:Myelin Basic Protein; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; C114843:incomplete Freund's adjuvant; D018664:Interleukin-12; D005620:Freund's Adjuvant