Abstract
Abstract Multiple sclerosis (MS) is a neurodegenerative disease with established autoimmune components. We described a unique T cell subset expressing CD40, Th40 cells that achieve effector status in autoimmune diseases. Furthermore we discovered that Th40 cells are detected in human subjects and that during autoimmunity these T cells are significantly (p < 10(-7) expanded in number compared to normal controls. Th40 cells produce both IFNg and IL-17, suggesting an interesting option for pathogenicity development. The majority of patients carried the DR15 (DR2) haplotype, but a significant number do not. Th40 cells were predominantly CD45RO (memory phenotype) and unlike Th40 cells in T1D express both CCR5 and CXCR3. In many patients, an antigen response profile was determined; i.e. some patients respond to MOG while others respond to PLP etc. In the EAE mouse model of MS we discovered that prior to EAE onset levels of Th40 cells are systemically very low, disease induction increased Th40 cell percentages and numbers drastically. When Th40 cells are isolated from EAE induced mice , disease can be adoptively transferred to scid recipients. Histology reveals that Th40 cells infiltrate brain and spinal cord. Th40 cells isolated from the brains of stage 3 EAE mice are pro-inflammatory.
Published Version
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