Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL/6 mice.
Encephalitogenic T cells that mediate experimental autoimmune encephalomyelitis (EAE) are commonly assumed to be exclusively CD4+, but formal proof is still lacking. In this study, we report that synthetic peptides 35-55 from myelin oligodendrocyte glycoprotein (pMOG(35-55)) consistently activate a high proportion of CD8+ alphabetaTCR+ T cells that are encephalitogenic in C57BL/6 (B6) mice. The encephalitogenic potential of CD8+ MOG-specific T cells was established by adoptive transfer of CD8-enriched MOG-specific T cells. These cells induced a much more severe and permanent disease than disease actively induced by immunization with pMOG(35-55). CNS lesions in pMOG(35-55) CD8+ T cell-induced EAE were progressive and more destructive. The CD8+ T cells were strongly pathogenic in syngeneic B6 and RAG-1(-/-) mice, but not in isogeneic beta2-microglobulin-deficient mice. MOG-specific CD8+ T cells could be repeatedly reisolated for up to 287 days from recipient B6 or RAG-1(-/-) mice in which disease was induced adoptively with <1 x 10(6) T cells sensitized to pMOG(35-55). It is postulated that MOG induces a relapsing and/or progressive pattern of EAE by eliciting a T cell response dominated by CD8+ autoreactive T cells. Such cells appear to have an enhanced tissue-damaging effect and persist in the animal for long periods.
Sun
D
D
Department of Neurology, and Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL 35294, USA. dsun@uab.edu
Whitaker
J N
JN
Huang
Z
Z
Liu
D
D
Coleclough
C
C
Wekerle
H
H
Raine
C S
CS
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002465:Cell Movement / Q000276:immunology; D002490:Central Nervous System / Q000473:pathology; D002908:Chronic Disease; D004254:DNA Nucleotidyltransferases / Q000172:deficiency / Q000235:genetics; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D012008:Recurrence; D045567:VDJ Recombinases; D014611:Vaccination
D018984:Epitopes, T-Lymphocyte; D018398:Homeodomain Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases