INTERACTION BETWEEN APOPTOTIC CELLS AND REACTIVE BRAIN-CELLS IN THE CENTRAL-NERVOUS-SYSTEM OF RATS WITH AUTOIMMUNE ENCEPHALOMYELITIS

To elucidate the role of brain cells in the immune regulation in the c entral nervous system (CNS). acute and chronic relapsing experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats and the l ocation of apoptotic inflammatory cells and their interaction with ast rocytes and microglia was investigated at Various stages of the diseas e. Apoptotic cells detected by terminal deoxynucleotidyl transferase-m ediated dUTP nick end-labeling (TUNEL) were few in number at day 10-12 post-immunization (PI), increased and peaked at day 13 PI. Then, thes e cells decreased gradually by day 21 PI. The most characteristic find ing was that apoptotic cells were: mainly distributed in the CNS paren chyma with only a few cells present in perivascular cuffs. Double stai ning by the TUNEL method and immunocytochemistry for astrocytes and mi croglia revealed. that astrocytes were more closely associated with ap optotic cells than microglia. Apoptotic cell death may be one mechanis m by which T cells are eliminated from the CNS. Furthermore, thr prese nt study suggests that astrocytes, rather than microglia, induce progr ammed cell death of infiltrating inflammatory cells. (C) 1998 Elsevier Science B.V.