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 central nervous system (CNS), acute and chronic relapsing experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats and the location of apoptotic inflammatory cells and their interaction with astrocytes and microglia was investigated at various stages of the disease. Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) were few in number at day 10-12 post-immunization (PI), increased and peaked at day 13 PI. Then, these cells decreased gradually by day 21 PI. The most characteristic finding was that apoptotic cells were mainly distributed in the CNS parenchyma with only a few cells present in perivascular cuffs. Double staining by the TUNEL method and immunocytochemistry for astrocytes and microglia revealed that astrocytes were more closely associated with apoptotic cells than microglia. Apoptotic cell death may be one mechanism by which T cells are eliminated from the CNS. Furthermore, the present study suggests that astrocytes, rather than microglia, induce programmed cell death of infiltrating inflammatory cells.