Interaction of immune and central nervous systems: contribution of anti-viral Thy-1+ cells to demyelination induced by coronavirus JHM.
The murine coronavirus JHM (JHMV or MHV-4) has been intensively studied as an experimental model of viral-induced demyelination; nonetheless, the degree to which demyelination results from direct viral cytolysis of oligodendroglia or immunological mechanisms remains controversial. To examine the contribution of immunity to the pathogenesis of JHMV in the central nervous system (CNS), mice were exposed to immunosuppressive doses of x-irradiation 3 days post infection and observed for clinical and pathological evidence of acute and subacute demyelination. Irradiated mice were found to have a nearly thousand-fold increase in central nervous system virus titer, as well as the presence of both abundant virus and viral antigen in white matter cells with the morphological characteristics of oligodendrocytes. Nonetheless, infected, irradiated mice had little or no evidence of demyelination or destruction of CNS cells. Adoptive transfers of spleen cells from syngeneic JHMV-immunized donors into irradiated JHMV-infected mice were carried out in order to determine the effect of immune reconstitution on pathogenesis. Splenocytes from JHMV-immune donors, but not naive donors or donors immunized with irrelevant antigen, completely restored demyelination in irradiated, JHMV-infected recipients. Depletion of Thy-1+ cells by treatment with monoclonal antibody and complement abolished the ability to transfer demyelination. We conclude that: 1) JHMV infection of the CNS does not result in acute or subacute demyelination in the absence of an intact immune response, and 2) viral-specific Thy-1+ cells are an essential element in the induction of demyelinating CNS lesions that result from JHMV infection.
Fleming
J O
JO
Department of Neurology, University of Wisconsin School of Medicine, Madison.
Wang
F I
FI
Trousdale
M D
MD
Hinton
D R
DR
Stohlman
S A
SA
D000818:Animals; D000954:Antigens, Surface; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D003333:Coronaviridae Infections / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D007107:Immune System / Q000473:pathology / Q000528:radiation effects; D016219:Immunotherapy, Adoptive; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D015213:Neuroimmunomodulation / Q000276:immunology* / Q000528:radiation effects; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens