The role of CD8 T cell avidity and specificity in ecperimental models of multiple sclerosis
Multiple sclerosis (MS) is the most common neurological disease of young adults. Clinical pathologies of MS are highly variable and dependent upon the parts of the central nervous system (CNS) affected. An animal model of CNS autoimmunity induced by CD4 T cells manifests many disease similarities to MS, however the pathologies of this model are a less diverse than those in MS patients. Recently, we have demonstrated that CD8 T cells can induce severe, demeylinating CNS autoimmunity that has many clinical and pathological similarities to human MS not seen in the CD4 T cell mediated model. CD8 T cells kill cells when the target cell is expressing the protein the T cell is reactive to. Thus, the variability in the MS lesion location and clinical symptoms may be a function of what cell types or location within the CNS the CD8 T cells is reactive to. Thus, the variability in MS location within the CNS the CD8 T cell are targeting. To test this hypothesis, disease pathologies will be compared when CD8T ecells are specifically targeting oligodendrocytes, neurons or astrocytes and when CD8 T cells specifically target cellls that reside in different anatomical locations of the CNS. A second set of experiments will compare the CNS protein specificty and reactivity patterns of studies have suggested that all individuals have CNS protein reactive T cells, however only a subset get MS. Delineating the nature of pathogenic T cells from non-pathogenic T cells is critical in understanding what drives the autoimmune process in MS.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.