Modulation of CNS autoimmune responses by CD8+ T cells coincides with their oligoclonal expansion

Abstract

MS is a highly prevalent neuroinflammatory disease of presumed autoimmune origin. Clinical observations and animal studies suggest that CD8+ T cells play an important role in MS but their exact mechanisms are ill defined. When we actively induced EAE in CD8 knock-out DA rats, or adoptively transferred encephalitogenic CD4+ T cells into CD8 knock-out DA rats, the disease course was indistinguishable from controls. Since our previous findings had revealed that the absence of CD8+ T cells in Lewis rats ameliorated EAE, we compared antigen-induced T cell differentiation in both strains. Disease onset and the composition of the draining lymph nodes were similar but T cell activation in DA rats was much weaker. Moreover, oligoclonal expansion of CD8+ T cells was exclusively observed in Lewis but not in DA rats. This suggests that myelin-specific CD8+ T cells are involved in the differentiation of encephalitogenic CD4+ T cells in Lewis rats, whilst they do not impact CD4+ T cell priming in DA rats. Hence, clonal expansion of CD8+ T cells in secondary lymphoid organs appears to be linked to their ability to modulate CNS autoimmune responses.