Comparison of a classical Th1 bacteria versus a Th17 bacteria as adjuvant in the induction of experimental autoimmune encephalomyelitis.

The relative contribution of myelin-specific Th1 and Th17 cells in the pathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), is controversial. IL-12, the key cytokine necessary for the differentiation of Th1 cells, has been found to be dispensable for EAE induction; while the related cytokine associated with Th17 cells, IL-23, is a critical factor for inducing EAE. Since EAE is induced by immunization with myelin proteins in CFA which contains M. tuberculosis that generates a prototypical Th1-mediated immune response, we sought to determine if replacing the M. tuberculosis in the adjuvant with a bacterium that induces an IL-23-dependent Th17 cell response during infection would induce EAE with a different phenotype. C. rodentium, a bacterium that requires IL-23 for protective immunity, was used as the adjuvant in EAE and compared to CFA. Mice immunized with C. rodentium adjuvant (CRA) developed classical signs of EAE, similar to CFA-immunized mice, but disease was less severe with a later onset and slower progression than CFA. Surprisingly, the peripheral cytokine profile revealed similar numbers of Th1 and Th17 cells for both CFA and CRA-immunized mice; however, the number of Th1 and Th17 cells was significantly reduced in the CNS of CRA-immunized mice. The development of EAE in CRA-immunized mice was associated with epitope spreading. The unique clinical course of CRA immunizations helps serve as a useful alternative model for studying EAE pathogenesis and potential therapeutics for MS.