Experimental Models Of Spontaneous In The Central Nervous System

Animal models have become essential tools for studying the human autoimmune disease. They are of vital importance in explorations of disease aspects, where, for diverse reasons, human material is unavailable. This is especially true for disease processes preceding clinical diagnosis and for tissues, which are inaccessible to routine biopsy. Early developing multiple sclerosis (MS) makes an excellent point in case for these limitations. Useful disease models should be developing spontaneously, without a need of artificial, adjuvant-supported induction protocols, and they should reflect credibly at least some of the complex features of human disease. The aim of this review is to compile models that exhibit spontaneous organ-specific autoimi-nunity and explore their use for studying MS. We first evaluate a few naturally occurring models of organ-specific autoimmune diseases and then screen autoimmunity in animals with compromised immune regulation (neonatal thymectomy, transgenesis, etc.). While most of these models affect organs other than the nervous tissues, central nervous system (CNS)specific autoirnmune disease is readily noted either after transgenic overexpression of cytokines or chemokines within the CNS or by introducing CNS-specific immune receptors into the lymphocyte repertoire. Most recently, spontaneous autoirnmunity resembling NIS was obtained by transgenic expression of self-reactive T cell receptors and B cell receptors. These transgenic models are not only of promise for studying directly disease processes during the entire course of the disease but may also be helpful in drug discovery.