Induction of autoimmune reactions to myelin basic protein in measles virus encephalitis in Lewis rats

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.

T cell memory specific for self and non-self antigens in rats persistently infected with Borna disease virus

“…Autoreactive T cells specific for MBP and PLP, the two major components of myelin proteins, were detected, although al a relatively low level compared wilh antiviral T cell reactivity. Such a myelin protein-directed self-reactivity of comparable magnitude has already been described in other models of virus-mediated encephalomyelitis in rats, e,g, in coronavirus- [7] and tneasles virus-induced encephalomyelitis [8], AutoreactiveTcellsshowedadefinite tendency to localize to the pt-LN and remain there for prolonged periods of time. The pl-LN are found in the thymic capsula in rats and in close proxitnity to the thymus on the capsula in mice [25].…”

“…Similar to cellular-mediated autoreactivity, antibodies with host-derived neuronal antigens have been described in different models of virus-triggered CNS diseases [8,18,19]. To determine a potential humoral response to MBP in Borna disease, sera of infected rats were tested in an en/yme-linked immunoassay.…”

“…e,g. coronavirus-induced encephalitis [7] or subacute measles encephalomyelitis [8]. BDV-infected animals were killed at day 25 after infection.…”

“…Examples comprise coronavirus-induccd cncephalomyelitis of Lewis rats [7]. characterized by marked demyelinating plaques and high titres of infectious virus, or measles-induced siibacute encephalotnyelitis in rats [8], where signs of detnyclination can hardly be observed. The contributions of these autoimmune reactions against myelin compotienls lo the respective imtnnnopathology rctnain therefore lo be determined.…”

Efficacy of individual measles virus structural proteins in the protection of rats from measles encephalitis

“…The MV-specific CMI in the presence of purified measles virions or purified MV structural proteins was analysed in single cell lymph node preparations obtained from animals immunized with the different VV recombinants before and after MV infection in a lymphoproliferation assay as described (Liebert et al, 1988). Briefly, single-cell suspensions (10 s to 3 x 105) from mesenteric lymph nodes were incubated with graded doses of MV antigens and control proteins for 72 h with an 18 h pulse of tritiated deoxythymidine (3HdT).…”