title: 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.
authors.affiliation: Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Henrike J
authors.initials: HJ
authors.lastname: Fischer
authors.affiliation: Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: van den Brandt
authors.affiliation: The DNA Microarray and Deep-Sequencing Facility Göttingen, University Medical Center Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lingner
authors.affiliation: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University Medical Center Göttingen, Waldweg 33, 37073 Göttingen, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Odoardi
authors.affiliation: Department of Neuroimmunology, Institute for Multiple Sclerosis Research, The Hertie Foundation and MPI for Experimental Medicine, University Medical Center Göttingen, Waldweg 33, 37073 Göttingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Flügel
authors.affiliation: Department of Neurology, University of Würzburg, Josef-Schneider-Straße 11, 97078 Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weishaupt
authors.affiliation: Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Humboldtallee 34, 37073 Göttingen, Germany. Electronic address: hreichardt@med.uni-goettingen.de.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D055786:Gene Knockout Techniques; D051381:Rats; D011917:Rats, Inbred Lew
keywords: CD8(+) T cells; EAE; Rats; TCR repertoire