Antigen and superantigen presentation in the human CNS

Abstract

Although the central nervous system (CNS) is often considered a site of relative immune privilege, this compartment has also long been recognized as a susceptible target of immune mediated disorders. The recognition of the clinical entity post-vaccination or acute disseminated encephalomyelitis (ADEM) established the precedent that systemic immunization with neural tissue could result in an inflammatory demyelinating disorder affecting the CNS. Studies of the animal disorder experimental autoimmune encephalomyelitis (EAE), initially developed to model ADEM ( Rivers et al., 1933 Rivers T.M. Sprunt D.H. Berry G.P. Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J. Exp. Med. 1933; 58 (Abstract): 39-53 Crossref PubMed Scopus (350) Google Scholar ), have now documented that such a disease process is initiated by antigen-specific T cells which are generated in the systemic compartment and then migrate to the CNS. Similar sequences of events are speculated to underlie the development of the human disease, multiple sclerosis (MS). The clinical and neuroimaging features of MS raise the further questions of what mechanisms account for the typical initial relapsing course of the disease, which then frequently acquires a superimposed progressive course. The initial relapsing disease course in MS is characterized by a high frequency of gadolinium enhancing lesions visualized by magnetic resonance (MR) imaging. The best available pathological data indicate that these magnetic resonance findings reflect an active lymphocyte dominated inflammatory response. In the chronic or progressive disease phase, lesions are dominated by macrophages and microglia. There is a relative paucity of lymphocytes. One does caution that there is likely heterogeneity of pathology in MS; such heterogeneity may correspond to distinct immunopathogenic mechanisms being operative in individual cases ( Lucchinetti et al., 1996 Lucchinetti C.F. Bruck W. Rodriguez M. Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol. 1996; 6: 259-274 Crossref PubMed Scopus (676) Google Scholar , Lassmann et al., 1998 Lassmann H. Raine C.S. Antel J. Prineas J.W. Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J. Neuroimmunol. 1998; 86: 213-217 Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar ). EAE and virus-induced immune mediated models, which more closely resemble the various clinical–pathological features of MS, continue to be developed.