Comparing the pathogenesis of experimental autoimmune encephalomyelitis in CD4-/- and CD8-/- DBA/1 mice defines qualitative roles of different T cell subsets.
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.
Abdul-Majid
Khairul Bariah
KB
Neuroimmunology Unit, Karolinska Hospital, SE-171 76 Stockholm, Sweden. kabdmaj2@jhmi.edu
Wefer
Judit
J
Stadelmann
Christine
C
Stefferl
Andreas
A
Lassmann
Hans
H
Olsson
Tomas
T
Harris
Robert A
RA
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D015704:CD4 Antigens / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016827:CD8 Antigens / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003711:Demyelinating Diseases / Q000517:prevention & control; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D017353:Gene Deletion; D015994:Incidence; D007271:Injections, Intradermal; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology
D001323:Autoantibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments