Different models of experimental autoimmune encephalomyelitis (EAE) have been successfully applied to investigate and manifold aspects of the autoimmune pathogenesis of multiple sclerosis. Studies using myelin-specific T-cell lines that transfer EAE to naive recipient animals established that only activated lymphocytes are able to cross the endothelial blood-brain barrier and cause autoimmune disease within the local parenchyma. All encephalitogenic T cells are CD4+ Th1-type lymphocytes that recognize autoantigenic peptides in the context of MHC class II molecules. In the case of myelin basic protein (MBP) specific EAE in the Lewis rat, the T-cell response is directed against one strongly dominant peptide epitope. The encephalitogenic T cells preferentially use one particular set of T-cell receptor genes. Although MBP is a strong encephalitogen in many species, a number of other brain protein are now known to induce EAE. These include mainly myelin components (PLP, MAG, and MOG), but also, the astroglial S-100 beta protein. Encephalitogenic T cells produce only inflammatory changes in the central nervous system, without extensive primary demyelination. Destruction of myelin and oligodendrocytes in these models requires additional effector mechanisms such as auto-antibodies binding to myelin surface antigens such as the myelin-oligodendrocyte glycoprotein.

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus and an aetiological agent of infectious mononucleosis, has a unique tropism for B lymphocytes. Clinical and laboratory features of chronic active EBV infections are chronic or persistent infectious mononucleosis-like symptoms and high antibody titre against early antigens (EA). Kawasaki disease (KD), aetiology unknown, is thought to be self-limited immunologically mediated vasculitis. Clinical features of KD are fever, rash, mucositis, lymphadenopathy and coronary artery damage. We report here a child with chronic active EBV infection accompanied by dilatation of coronary arteries. All the EBV-determined nuclear antigen (EBNA)-positive lymphocytes had exclusively CD4 antigen, as revealed by dual staining immunofluorescence analysis. Southern blot hybridization showed that the purified CD4+ cells harboured EBV genome.

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The pathogenic potential of autoimmune T cell responses to nonmyelin autoantigens was investigated in the Lewis rat using the astrocyte-derived calcium binding protein S100 beta, as a model nonmyelin autoantigen. The Lewis rat mounts a vigorous RT1B1 (major histocompatibility complex class II) restricted autoimmune response to an immunodominant S100 beta epitope (amino acid residues 76-91). The adoptive transfer of S100 beta-specific T cell lines induced a severe inflammatory response in the nervous system, but only minimal neurological dysfunction in naive syngeneic recipients. The inability of S100 beta-specific T cell transfer to induce severe disease was associated with a decreased recruitment of ED1+ macrophages into the central nervous system (CNS) in comparison with that seen in severe experimental autoimmune encephalomyelitis (EAE) induced by the adoptive transfer of myelin basic protein (MBP)-specific T line cells. Moreover, unlike encephalitogenic MBP-specific T cell lines, S100 beta-specific T cell lines exhibited no cytotoxic activity in vitro. Histopathological analysis also revealed striking differences in the distribution of inflammatory lesions in MBP- and S100 beta-specific T cell-mediated disease. In contrast to the MBP paradigm, S100 beta-specific T cell transfer induces intense inflammation not only in the spinal cord, but throughout the entire CNS and also in the uvea and retina of the eye. In view of the distribution of lesions throughout the grey and white matter of the CNS we propose to term this new model experimental autoimmune panencephalomyelitis (EAP) to differentiate it from EAE. These experiments demonstrate for the first time that nonmyelin CNS autoantigens can initiate a pathogenic autoimmune T cell response, although the nature of the target autoantigen profoundly influences the clinical and histopathological characteristics of the resulting autoimmune disease. This is not simply a consequence of the distribution of the autoantigen, as both MBP and S100 beta are coexpressed in many areas of the CNS, but reflects differences in the capacity of different regions of the CNS to process and present specific autoantigens. This new model of T cell-mediated autoimmune CNS disease exhibits a number of similarities to multiple sclerosis (MS), such as its mild clinical course and the involvement of areas of the brain and eye, which are absent in myelin-mediated models of EAE. Nonmyelin autoantigens may therefore play an unexpectedly important role in the immunopathogenesis of inflammatory diseases of the CNS.