Coexpression of Fas/FasL and Bax on brain and infiltrating T cells in the central nervous system is closely associated with apoptotic cell death during autoimmune encephalomyelitis

Recent studies have suggested that autoimmune inflammation elicited in the central nervous system (CNS) is subsided by apoptotic cell death of inflamm atory cells. To elucidate the molecular mechanism of apoptosis of infiltrat ing T and other cells occurring in the CNS during autoimmune encephalomyeli tis, we determined the type of apoptotic cells and the localization of apop tosis-related molecules (Fas, FasL, Bax, Bcl-2 and active caspase 3) by imm unohistochemistry. Double labeling with the TUNEL method and cell-type mark ers showed that infiltrating T cells and microglia/macrophages underwent ap optosis, while astrocytes and neurons did not. Staining for apoptosis-relat ed molecules revealed that infiltrating T cells and microglia/macrophages, but not astrocytes and neurons, expressed both Fas-FasL and Bax. The distri bution and cell type of active caspase 3-positive cells were essentially th e same as those of TUNEL-positive cells. These findings suggest that coexpr ession of Fas/FasL and Bax is closely associated with apoptotic cell death of infiltrating T cells and microglia in the CNS. Furthermore, astrocytes w hich express Fas and FasL, but not Bax, may play an important role in regul ating inflammation in the CNS by inducing apoptotic cell death of infiltrat ing T cells and microglia, both of which have an inflammation-promoting nat ure. (C) 2000 Elsevier Science B.V. All rights reserved.