Target antigens in the central nervous system

A U ' I ~ ~ , T CELLS AND IMMUNE REGULATION Yehuda Shoenfeld Research Unit of Autoimmune Diseases, Department of Medicine 'B' Sheba Medical Center, Tel-Hashomer, Israel The etiology of autoimmone diseases is multifaetorial entailing genetic~ immunological, hormonal and environmenud factors. The hallmark of autoimmune conditions consi~t of autoantibodies or autoreactive T cells. Yet, there are many situations in which autoantibodies can be detected (e.g. healthy individuals, first degree relatives, monoclonal gammopathies) and the subjects are asymptomatic. The pathogenetic role which breaks tolerance may be due to the emergence of p~thogenic idiotypes, immunoglubolin class switch (lgM to IgG), high avidity autoantibo~l!es, cr monospecific vs, poly specific autoantibodies. One of the main immune dysregulations reported in all autoimmune diseases is T suppressor cell defects, which include both low number as well as defect in function. We will present a new model of SLE in which we induced the disease in naive mice with a pathogenic anti-DNA idiotype and prevented the induction by specific 'Is cell manipulation. The importance of pathogenic idiotypes and Ts cell defects in immuneregulation, tolerance and autoimmunity will be discussed. 1. Shoenfeld Y, lsanberg DA (authors) the Mosaic of Autoimmunity. Elsevier, The Netherlands, 1989. 2. Shoenfeld Y, Mozes E. Pathogenic idiotypes of autoantibodies in autoimmonity: Lessons from new experimental models of SLE. FASEB 4; 2646, 1990. 3. Blank M, Ben-Bassat M, Shoenfeld Y. Modulation of experimental SLE with Ts specific for a pathogenic idiotype. CeIL Immunol (in press). TARGET ANTIGENS IN TI-r~ CENTRAL NERVOUS SYSTEM Takeshi Tabira National Institute of Neurosciance, Kodaira, Tokyo 187, Japan . Autoimmune mechanisms are postulated in para-nceplastic syndrome such as limbie encephalitis, Yo syndrome, CAR syndrome, motomeuron disease, and others. In these, CDR34, CDR62, PCDIT, p26, GM1 ganglioside and other antigens are identified. In addition, autoimmune disorders without malignant tumors are known. These are autoimmune hypophysitis and stiff-man syndrome. In the latter, immune reactions to giutamic acid decarboxylase are known. Furthermore, immunization with autonomic nerves or acetylcholine esterase inducc~ experimental autoimmuna autonomic disorders, and that with motor neurons induces experimental autoimmune motomeuron disease. In Alzheimer disease, immune competent cells are present in the brain and auto antibodies to eholinergic neurons and others are elevated, but the significance of these immune reactions are unknown. In demyelinating diseases such as multiple sclerosis and acute disseminated encephalomyelitis, myelin basic protein (MBP), proteolipid protein (PLP), and myelinoligodendrocyte glycoprotein (MOG) are supposed to be target antigens. MBP- and PLPinduced autoimmune mechanisms are well characterized in experimental autoimmune encephalomyelitis (EAE), in which a role of heatshock protein is postulated to be involved.