Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen

Abstract

The role of infection in the pathogenesis of clinical relapses that occur in most autoimmune diseases, including multiple sclerosis, remains to be established. Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis, with episodes of relapsing paralysis. In certain strains of mice, T-lymphocytes expressing the V beta 8 T-cell receptor (TCR) engage the amino-terminal epitope Ac1-11 of myelin basic protein, leading to EAE. The bacterial superantigen staphylococcal enterotoxin B (SEB) activates V beta 8-expressing T cells. Here we show that after immunization with Ac1-11, or after transfer of encephalitogenic T-cell lines or clones reactive to Ac1-11, SEB induces exacerbation or relapses of paralytic disease in mice that are in clinical remission following an initial episode of paralysis, and triggers paralysis in mice with subclinical disease. Tumour necrosis factor has a critical role in the mechanism underlying SEB-induced exacerbation of disease, because anti-tumour necrosis factor antibody given in vivo delays the onset of paralysis triggered by SEB. On reactivation of autoaggressive cells through their T-cell receptor, superantigens may induce clinical relapses of autoimmune disease.

Does the Frequency and Avidity Spectrum of the Neuroantigen-Specific T Cells in the Blood Mirror the Autoimmune Process in the Central Nervous System of Mice Undergoing Experimental Allergic Encephalomyelitis?

“…By the time of recovery, there might not be sufficient MBP:87-99-specific blasts present in the immune periphery to fuel the autoimmune attack on the CNS although there apparently still are sufficient numbers of (resting) Ag-experienced memory/effector cells left. When reactivated in vitro for adoptive transfers, or reactivated in vivo by superantigens (33), these "ignorant" Ag-experienced memory/effector cells can become pathogenic. Gradual loss of the hyperactivated state of the first generation of effector cells (MBP:87-99-specific T cells in MBP:87-99-induced EAE), therefore, might account for the initial recovery from EAE.…”

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

“…Several mechanisms have been postulated to explain this phenomenon. These include the release of self-antigens or cryptic or new antigenic determinants in the target organs leading to the generation of pathogenic CD4 T cells (Miller et al, 1997), bystander activationofautoaggressive T cells by superantigens (Brocke et al, 1993), and molecular mimicry in which structural homologies between self and foreign antigens facilitate the recognition of self tissues by cross-reactivity (Wucherpfennig and Strominger, 1995).…”

Mechanisms for the induction of autoimmunity by infectious agents

“…The majority of T cells specific for this peptide express Vβ8, allowing activation of such T cells by the superantigen staphylococcal enterotoxin B. Administration of this superantigen causes relapses and exacerbation of EAE (14), but it has not been possible to induce EAE by superantigen administration. On the contrary, injection of superantigen prior to immunization with MBP prevents the development of EAE in PL/J mice due to deletion of T cells that express Vβ8 (15).…”

“…Peptides from microbial proteins that have sufficient structural similarity with self-peptides can activate autoreactive T cells, a mechanism that is referred to as molecular mimicry (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Microbial superantigens activate large numbers of T cells that express particular Vβ gene segments, and a subpopulation of these activated cells can be specific for a self-antigen (13)(14)(15)(16)(17). The inflammatory setting that results from a viral or bacterial infection leads to local activation of antigen-presenting cells and can result in enhanced processing and presentation of self-antigens present at that site.…”