title: Comparison of a classical Th1 bacteria versus a Th17 bacteria as adjuvant in the induction of experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH 43210, United States.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Peng
authors.forename: Rachel
authors.initials: R
authors.lastname: Beers
authors.forename: Michael K
authors.initials: MK
authors.lastname: Racke
authors.forename: Amy E
authors.initials: AE
authors.lastname: Lovett-Racke
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D044082:Citrobacter rodentium / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000382:microbiology*; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology*; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000276:Adjuvants, Immunologic; D053759:Interleukin-23; D018664:Interleukin-12