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Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats
U G Liebert1, C Linington, V ter Meulen
1Institut für Virologie und Immunbiologie, Universität Würzburg, F.R.G.
Abstract:
Intracerebral inoculation of weanling Lewis rats with measles virus led to the development of subacute measles encephalomyelitis (SAME) 4-8 weeks after infection. The disease is characterized pathologically by an intense inflammatory infiltration within both the white and grey matter of the central nervous system (CNS) without apparent demyelination. Both during and after SAME splenic lymphocytes from these animals could be restimulated in vitro to proliferate in the presence of myelin base protein (MBP). MBP-specific class II MHC-restricted T cell lines were isolated from this cell population. They were shown to exhibit no cross-reactivity with measles virus and to induce experimental allergic encephalitis (EAE) in naive syngeneic recipients following adoptive transfer. The clinical and histopathological signs of this T cell-mediated disease were identical to that seen in classical T cell-mediated EAE. A humoral immune response to MBP was only detected in a limited number of those rats with SAME. These results indicate that autoimmune reactions to brain antigen can arise during measles virus infection which may contribute to the pathogenesis of measles virus-associated encephalomyelitis.
Insights
Measles virus infection in rats triggers an autoimmune response targeting myelin basic protein (MBP), leading to subacute measles encephalomyelitis (SAME). This T cell-mediated disease mimics experimental allergic encephalitis (EAE).
Area of Science:
- Neuroimmunology
- Virology
- Autoimmunity
Background:
- Measles virus infection can cause central nervous system (CNS) inflammation.
- Subacute measles encephalomyelitis (SAME) is characterized by CNS inflammation without demyelination.
Purpose of the Study:
- To investigate the potential autoimmune mechanisms underlying measles virus-associated encephalomyelitis.
- To determine if measles virus infection induces autoimmune responses to brain antigens.
Main Methods:
- Intracerebral inoculation of Lewis rats with measles virus to induce SAME.
- In vitro restimulation of splenic lymphocytes with myelin basic protein (MBP).
- Isolation and characterization of MBP-specific T cell lines.
- Adoptive transfer of T cell lines to induce experimental allergic encephalitis (EAE) in naive rats.
Main Results:
- Rats with SAME developed splenic lymphocytes that proliferated in response to MBP.
- MBP-specific, class II MHC-restricted T cell lines were isolated and induced EAE upon transfer.
- These T cell lines did not cross-react with measles virus.
- A humoral immune response to MBP was detected in only a few SAME rats.
Conclusions:
- Measles virus infection can trigger autoimmune reactions against brain antigens like MBP.
- These autoimmune responses, mediated by T cells, likely contribute to the pathogenesis of measles virus-associated encephalomyelitis.
- The findings suggest a mechanism for post-infectious CNS autoimmunity.