Selective and antigen-dependent effects of myelin degeneration on central nervous system inflammation.
Damage to myelin sheath or oligodendrocytes may precede or even provoke inflammation of the central nervous system (CNS), but the extent to which these degenerative changes affect inflammation remains largely undefined. To study these processes in more detail, we used CNS antigen-specific T cells in the presence or absence of anti-myelin antibodies to induce experimental autoimmune encephalomyelitis (EAE) in transgenic Lewis rats with low-grade subclinical myelin degeneration and associated microglia cell activation, and in wild-type Lewis rats with an intact CNS. We found that myelin degeneration affects the localization of inflammatory lesions, the numbers of T cells recruited to these lesions, and the severity of the resulting clinical disease. In addition, myelin degeneration and associated microglia cell activation jointly enhance the susceptibility of the CNS to the action of anti-myelin antibodies. Our data show that even subtle alterations of myelin and oligodendrocytes may massively amplify the extent of demyelination and tissue damage, involving different immune effector mechanisms. A similar causal relationship might also operate in human patients with multiple sclerosis, where T cell-mediated inflammation and antibody-mediated demyelination have been documented, and where genetic factors might determine the susceptibility of the target tissue for immune-mediated injury.
Aboul-Enein
Fahmy
F
Medizinische Universität Wien, Institut für Hirnforschung, Abteilung Neuroimmunologie, Austria.
Bauer
Jan
J
Klein
Matthias
M
Schubart
Anna
A
Flügel
Alexander
A
Ritter
Thomas
T
Kawakami
Naoto
N
Siedler
Frank
F
Linington
Christopher
C
Wekerle
Hartmut
H
Lassmann
Hans
H
Bradl
Monika
M
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D000939:Epitopes; D005260:Female; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009186:Myelin Sheath / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D000941:Antigens; D000939:Epitopes; D018991:Myelin Proteolipid Protein