摘要:

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by infiltration of T lymphocytes and macrophages into white matter leading to demyelination [1-2]. This pathology is frequently associated with disability of neurological function, in particular sensory deficits, visual problems and paralysis. The acute MS plaques are markered by the presence of activated T cells expressing the IL-2 receptor as well as activated, class II MHC positive macrophages [3-4]. In addition, cytokines such as TNF and oligoclonal immunoglobulin have been found in the brain and cerebrospinal fluid (CSF) of patients with MS [5-7]. This active inflammatory process is confined to the CNS, not affecting either the peripheral nervous system or other organs. Although it is generally accepted that this CNS inflammatory process causes demyelination and the resulting neurologic disability in MS, the mechanism(s) by which the inflammation is initiated and maintained is unknown.

ISSN:0883-0185    

DOI:10.3109/08830189209061790

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The effects of neuroantigen-specific tolerance on the induction and effector stages of EAE were examined. Tolerance induced by the i.v. injection of syngeneic splenocytes coupled with purified neuroantigens or encephalitogenic peptides of MBP and PLP using ethylene carbodiimide was extremely effective in both prevention and treatment of acute and relapsing forms of EAE in Lewis rats and SJL/J mice. The unresponsiveness is rapidly-induced, dose-dependent, long-lasting, efficient, MHC class II-restricted, and exquisitely antigen-specific. This procedure targets only effector cells bearing clonotypic receptors specific for the autoantigen/ autoepitope and thus does not depend upon the autoimmune response being dominated by a restricted T cell repertoire. Moreover, it does not require that the response to the autoantigen be dominated by recognition of a specific epitope(s) within a particular autoantigen, or even the identification of the specific autoantigen. The results also demonstrate the usefulness of peripheral tolerance induced by antigen-coupled syngeneic splenocytes for identifying the fine specificity of autoimmune T cell responses which appear to change during the progression of relapsing EAE. Thus, this technique offers major advantages over many other currently employed immunoregula-tory strategies and is therefore relevant for establishment of therapeutic protocols for the antigen-specific treatment of human T cell-dependent autoimmune disorders.

ISSN:0883-0185    

DOI:10.3109/08830189209061791

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189209061792

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189209061793

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor