Lymphocytes from mice chronically infected with Theiler's murine encephalomyelitis virus produce demyelination of organotypic cultures after stimulation with the major encephalitogenic epitope of myelin proteolipid protein. Epitope spreading in TMEV infection has functional activity.
Theiler's murine encephalomyelitis virus (TMEV) infection produces a chronic inflammatory disease of the spinal cord white matter, with striking similarities to both experimental allergic encephalomyelitis (EAE) and human multiple sclerosis (MS). The first phase of demyelination in this model appears to be dependent on a delayed-type hypersensitivity (DTH) response to viral antigens, driven by CD4+, Th1 lymphocytes. Macrophages, recruited in the infected CNS, would be responsible for most of the myelin damage. Recently, new populations of CD4+ lymphocytes were demonstrated in infected mice, this time with specificity for myelin antigens, particularly PLP. This suggests that, in the chronic phase of the disease, an autoimmune mechanism of demyelination, similar to EAE, may participate in the process of myelin destruction. The present study represents a first step in exploring the functional activity of these anti-myelin lymphocytes that emerge during the chronic phase of the disease. Lymphocytes were removed from chronically infected animals, they were stimulated with the major PLP encephalitogenic epitope for SJL/J mice, and they were added to organotypic myelinated spinal cord cultures for different lengths of time. Results show that lymphocytes stimulated with the major PLP epitope have a powerful capacity for demyelinating these cultures, while MBP stimulated lymphocytes and lymphocytes from control animals do not. This study, suggests that the anti-myelin response that emerges during the chronic phase of the infection is functionally active. A similar phenomenon of epitope spreading from virus to organ specific antigens may take place in humans and be involved in a number of immune-mediated diseases, including MS.
Dal Canto
M C
MC
Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA. m-dalcanto@.nwu.edu
Calenoff
M A
MA
Miller
S D
SD
Vanderlugt
C L
CL
D000818:Animals; D018188:Cardiovirus Infections / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology*; D004660:Encephalitis / Q000276:immunology; D000939:Epitopes / Q000494:pharmacology; D007114:Immunization; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000494:pharmacology; D018991:Myelin Proteolipid Protein / Q000276:immunology / Q000494:pharmacology*; D009186:Myelin Sheath / Q000502:physiology*; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000276:immunology; D017945:Theilovirus
D000939:Epitopes; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010047:Ovalbumin