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Abstract: Inducible nitric oxide synthase (NOS2) expression in the central nervous system correlates with EAE disease activity. Inhibition of NOS2 ameliorates adoptively transferred EAE, yet exacerbates actively induced EAE. Herein, the encephalitogenicity of T cells induced by immunization in the presence or absence of NOS2 was examined. Upon passive transfer, T cells from myelin oligodendrocyte glycoprotein-immunized NOS2-deficient C57BL/6 mice induced more severe EAE than T cells from wild-type mice. The heightened encephalitogenicity of NOS2−/− T cells correlated with enhanced expression of VLA-4 (CD49d) and increased production of interferon gamma and tumor necrosis factor. NO plays an important regulatory role in autoimmune T cell induction. [Copyright &y& Elsevier]

Previous work demonstrated that EAE induced by recombinant human MOG was B cell-dependent. Data presented here reveal a T cell response to MOG61–85 in human rMOG-immunized B cell −/− mice not observed in WT mice. Further study revealed this peptide to be a cryptic epitope in WT mice. Co-immunization of B cell −/− mice with MOG35–55 and MOG61–85 peptides led to less severe disease compared to mice immunized with MOG35–55 alone. Disease amelioration was associated with decreased production of Interferon-γ by lymph node cells. Thus, MOG61–85 represents a protective epitope to human rMOG induced EAE in B cell −/− mice. [ABSTRACT FROM AUTHOR]