Browsing by Author "Mostarica-Stojkovic, M. (6701741422)"

[No abstract available]

Experimental autoimmune encephalomyelitis (EAE) is a well-recognized model for multiple sclerosis (MS) in humans. However, adjuvants used with encephalitogens to induce EAE produce non-specific effects interfering with the mechanisms involved in the autoimmune response to the central nervous system (CNS) tissue. It is therefore important to establish a more suitable model of EAE for analysis of autoimmune phenomena resembling those operative in MS. Here we report that EAE can be induced regularly in Dark Agouti (DA) strain of rats with spinal cord tissue without any adjuvant, as judged by both clinical and histological parameters. The incidence and severity of EAE depended on the origin of the encephalitogen, the rat versus guinea pig spinal cord homogenate being more efficient. Furthermore, EAE could be reinduced in animals which had recovered from disease that had been induced actively with encephalitogen alone, suggesting the role of adjuvant-generated non-specific mechanisms in resistance to reinduction of EAE. Thus, EAE induced in DA rats with encephalitogen alone provides a reproducible model for defining pathogenically relevant events in CNS autoimmunity devoid of the potentially misleading effects of adjuvants.

Susceptibility to the induction of EAE was compared in AO, DA and Lewis strain of rats. As evaluated by clinical and histological criteria, AO rats exhibited significantly lower susceptibility to EAE induced with guinea-pig spinal cord (GPSC) tissue and complete resistance to the encephalitogenic challenge with rat myelin basic protein (BP) irrespective of antigen dose and adjuvant used. AO rats pre-treated with BP + Freund's incomplete adjuvant became completely unresponsive to the induction of EAE with GPSC + Freund's complete adjuvant (FCA) indicating that they do possess cells sensitive to some antigenic determinants of rat BP. In order to test whether the resistance to EAE is due to an active suppression, low dose of irradiation (300 rad) and cyclophosphamide (20 mg/kg) was applied prior to the induction of EAE. Selective depletion of radiosensitive cells facilitated the induction of EAE. Similarly, cyclosphosphamide given 2 days prior to BP + FCA completly abrogated the resistance to EAE induction. Thus, it appears that the inability of BP + FCA to produce EAE in AO rats is due to the disproportionate activation of suppressor cells.

Helminth infection has a potent systemic immunomodulatory effect on the host immune response, which also affects the development of autoimmune diseases. We investigated the dose-dependent influence of Trichinella spiralis infection on experimental autoimmune encephalomyelitis (EAE). Our model of concomitant T. spiralis infection and EAE demonstrates that established infection of Dark Agouti (DA) rats with the parasite causes amelioration of the clinical course of induced EAE in a dose-dependent way. Infection with T. spiralis L1 stage muscle larvae (TSL1) reduced the severity of the autoimmune disease as judged by lower maximal clinical score, cumulative index, duration of illness and degree of mononuclear cell infiltration in T. spiralis infected animals compared to control, EAE-induced group. This study provides a valuable model of worm infection to investigate helminth-induced regulatory mechanisms for optimal benefit to the host. © 2008 Elsevier Inc. All rights reserved.

Helminth infection has a potent systemic immunomodulatory effect on the host immune response, which also affects the development of autoimmune diseases. We investigated the dose-dependent influence of Trichinella spiralis infection on experimental autoimmune encephalomyelitis (EAE). Our model of concomitant T. spiralis infection and EAE demonstrates that established infection of Dark Agouti (DA) rats with the parasite causes amelioration of the clinical course of induced EAE in a dose-dependent way. Infection with T. spiralis L1 stage muscle larvae (TSL1) reduced the severity of the autoimmune disease as judged by lower maximal clinical score, cumulative index, duration of illness and degree of mononuclear cell infiltration in T. spiralis infected animals compared to control, EAE-induced group. This study provides a valuable model of worm infection to investigate helminth-induced regulatory mechanisms for optimal benefit to the host. © 2008 Elsevier Inc. All rights reserved.