Autoimmune neurologic diseases

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Myelin-specific cd8+ T Cells Exacerbate Cns Autoimmunity and Increase Clinical Signs of Brain Inflammation

Thursday, June 15
5:45 PM - 7:00 PM

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). Although the pathogenic pathways of MS are not fully understood, myelin-specific CD4+ T cells are hypothesized to initiate disease. However, substantial data from MS patients indicate that CD8+ T cells also contribute to MS pathogenesis. We hypothesized that recruitment of myelin-specific CD8+ T cells to the site of inflammation initiated by CD4+ T cells will influence disease. To test our hypothesis, we use a mouse model of MS, experimental autoimmune encephalomyelitis (EAE) in which we initiate disease by adoptive transfer of CD4+ T cells specific for myelin oligodendrocyte glycoprotein (MOG). To determine the influence of CD8+ T cells, we induced disease in TCR-transgenic mice that express a TCR specific for a MHC class I-restricted epitope of myelin basic protein (MBP), or in wild-type mice that also received an injection of naïve CD8+ T cells from the TCR-transgenic mouse. We found that the recruitment of the MBP-specific but not control CD8+ T cells exacerbated EAE. Strikingly, MBP-specific CD8+ T cells increased symptoms associated with brain inflammation. Increased disease severity was associated with a higher number of MOG-specific CD4+ T cells within the brain and spinal cord. Furthermore, MBP-specific CD8+ T cells produced more TNFa and in the brain and spinal cord as compared to WT CD8+ T cells. These data suggest that the interplay between CD4+ and CD8+ T cells specific for two different myelin proteins is critical for determining the manifestation of CNS autoimmune disease.

Catriona A. Wagner

Graduate Student
University of Washington

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    Joan Goverman

    University of Washington

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