Interferon-gamma in progression to chronic demyelination and neurological deficit following acute EAE.
The cytokine interferon-gamma (IFNgamma) is implicated in the induction of acute CNS inflammation, but it is less clear what role if any IFNgamma plays in progression to chronic demyelination and neurological deficit. To address this issue, we have expressed IFNgamma in myelinating oligodendrocytes of transgenic mice. MHC I immunostaining and iNOS mRNA were upregulated in their CNS, but such transgenic mice showed no spontaneous CNS inflammation or demyelination, and the incidence, severity, and histopathology of experimental autoimmune encephalomyelitis (EAE) were similar to nontransgenic controls. In contrast to control mice, which remit from EAE with resolution of glial reactivity and leukocytic infiltration, transgenics showed chronic neurological deficits. While activated microglia/macrophages persisted in demyelinating lesions for over 100 days, CD4(+) T lymphocytes were no longer present in CNS. IFNgamma therefore may play a role in chronic demyelination and long-term disability following the induction of demyelinating disease. Because IFNgamma may have neural as well as immune-infiltrating origins, these findings generate a new perspective on its role in the CNS.
Renno
T
T
Neuroimmunology Unit, Montreal Neurological Institute, 3801 University, Montreal, Quebec, H3A 2B4, Canada.
Taupin
V
V
Bourbonnière
L
L
Verge
G
G
Tran
E
E
De Simone
R
R
Krakowski
M
M
Rodriguez
M
M
Peterson
A
A
Owens
T
T
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000276:immunology*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D015870:Gene Expression / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis; D008264:Macrophages / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000737:chemistry / Q000276:immunology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis
D017252:CD3 Complex; D016177:Macrophage-1 Antigen; D012333:RNA, Messenger; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens