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

J Neuroimmunol. 2016 Jan 15;290:26-32. doi: 10.1016/j.jneuroim.2015.10.020. Epub 2015 Oct 29.


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.

Keywords: CD8(+) T cells; EAE; Rats; TCR repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer* / methods
  • Animals
  • Autoimmunity / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / transplantation
  • Central Nervous System / immunology
  • Central Nervous System / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Gene Knockout Techniques
  • Rats
  • Rats, Inbred Lew