Bm. Segal et al., CPG oligonucleotides are potent adjuvants for the activation of autoreactive encephalitogenic T cells in vivo, J IMMUNOL, 164(11), 2000, pp. 5683-5688
The mechanism of action of microbial adjuvants in promoting the differentia
tion of autoimmune effector cells remains to be elucidated. We demonstrate
that CpG-containing oligodeoxynucleotides (ODN) can completely substitute f
or heat-killed mycobacteria in the priming of encephalitogenic myelin-react
ive T cells in vivo. The adjuvanticity of the CpG ODN was secondary to thei
r direct ability to induce IL-12 or to act synergistically with endogenous
IL-12 to promote Th1 differentiation and encephalitogenicity. T cells prime
d in the absence of CpG with Ag and IFA alone appeared to be in a transitio
nal state and had not undergone differentiation along a conventional Th pat
hway. Unlike Th2 cells, they expressed low levels of the IL-12R beta 2 subu
nit and retained the ability to differentiate into encephalitogenic effecto
rs when reactivated in vitro under Th1-polarizing conditions. These results
support the use of CpG ODN as adjuvants but also suggest that they could p
otentially trigger autoimmune disease in a susceptible individual.