Introduction

The cause of multiple sclerosis (MS) is unknown. MS is unevenly distributed and in countries with high prevalence, approximately 1 in 1,000 is affected. MS affects mostly young adults and results in considerable disability and suffering. It is currently very much a forgotten disease, where the severely affected victims fade away in nursing homes, unable to promote their case or motivate the society to any greater involvement. Until recently, no effective treatment that alters the course of MS in a desirable way has been available. Now, much hope is focused on interferon$ (IFN-P) (1). Unfortunately, preliminary data from three years follow-up of treated patients have not revealed any difference in disability compared to untreated patients (Ebers, personal communication). MS affects principally the white matter of the central nervous system (CNS). The gross pathology is characterized by plaques that appear as scattered, irregularely shaped, usually circumscribed, translucent gray areas 1-15 mm in diameter. The sites of predilection in the brain include the white matter bordering the ventricles where extensive, confluent lesions may be found. Lesions are also frequent in the optic nerves and cervical spinal cord (2). Histopathologically, lesions found in chronic MS correspond to astrocytic scar tissue, respresenting an end stage of an inflammatory disease process during which myelin and oligodendrocytes are selectively destroyed while axons are relatively spared. Depending on the degree of inflammation and the appearance of the lesion edge, plaques can be classified as acute, active chronic and silent chronic ( 3 ) . The inflammatory infiltrates contain lymphocytes, macrophages and plasma cells. Immunocytochemical studies have revealed CD4+, CD8+ and IL-2R+ cells preferentially at the edge of plaques, while macrophages are most numerous in the center. Oedematous white matter containing macrophages and irregularely contoured myelin sheaths have been claimed to reflect the earliest discernible white matter lesion (4). It is not clear when T and B lymphocytes appear in very early, acute lesions. The perivenous loss of myelin with axonal preservation found in MS is otherwise seen only in perivenous encephalomyelitis following virus infections and rabies vaccination (2). The mechanism responsible for myelin breakdown in MS is unclear. Ultrastructural studies indicate that myelin destruction is mediated by macrophages (5). As visualized in Fig. 1, many of the immunopathologic features in MS lesions such as astrogliosis, macrophage activation, major histocompatibility complex (MHC) induction and T cell homing have been claimed to fit with known effects of IFN-y (6). A generally accepted immunological abnormality in MS is the vigorous B cell response confined to the cerebrospinal fluid (CSF) and characterized by a mild mononuclear pleocytosis in about half of the patients, elevated IgG index in about 70% and oligoclonal IgG bands in CSF while not detectable in the patient's serum in practically every MS patient (reviewed in 7,8). Elevated IgG index and oligoclonal bands reflect an augmented B cell response within the CNS, the origin of which has remained enigmatic. It is compatible with an infectious etiology. A variety of infectious agents have been proposed to cause MS, including herpes simplex and parainfluenza virus, but all claims hitherto made have been refuted (reviewed in 9). Nevertheless, elevated concentrations of locally produced antibodies to a variety of viruses is characteristic for MS CSF (lo), although there is only minimal comigration between oligoclonal bands and viral antibodies. The observation that viral infections pre-