J Neuroimmunol. 2003 Aug;141(1-2):10-9
Abdul-Majid KB, Wefer J, Stadelmann C, Stefferl A, Lassmann H, Olsson T, Harris RA.
Neuroimmunology Unit, L8:04 CMM, Karolinska Hospital, SE-171 76, Stockholm, Sweden
Experimental autoimmune encephalomyelitis (EAE) was induced with myelin oligodendrocyte glycoprotein (MOG(1-125)) in CD4(-/-) and CD8(-/-) DBA/1 mice.
Both gene-deleted mice developed clinical signs of EAE, albeit milder than in wild-type mice, suggesting that both CD4(+) and CD8(+) cells participate in disease development.
Demyelination and inflammation in the central nervous system was reduced in the absence of CD8(+) T cells.
Antibody depletion of CD4(+) cells completely protected CD8(-/-) mice from MOG-induced EAE while depletion of CD8(+) cells in CD4(-/-) mice resulted in fewer EAE incidence compared to that in control antibody-treated mice.
Antibody depletion of CD4(+) cells in wild-type mice protected from EAE, but not depletion of CD8(+) cells, although demyelination was reduced on removal of CD8(+) T cells.
Immunization with immunodominant MOG(79-96) peptide led to EAE only in the presence of pertussis toxin (PT) in the inoculum.
PT also triggered an earlier onset and more severe EAE in CD8(-/-) mice.
We interpret our findings such that in an ontogenic lack of CD4(+) T cells, EAE is mediated by CD8(+) and elevated levels of alphabetaCD4(-)CD8(-) cells, and that CNS damage is partly enacted by the activity of CD8(+) T cells.