T-cell-based immunity counteracts the potential toxicity of glutamate in the central nervous system

Injuries to the central nervous system (CNS) evoke self-destructive process es, which eventually lead to a much greater loss of tissue than that caused by the trauma itself. The agents of self-destruction include physiological compounds, such as glutamate, which are essential for the proper functioni ng of the CNS, but become cytotoxic when their normal concentrations are ex ceeded. The CNS is equipped with buffering mechanisms that are specific for each compound. Here we show, using Balb/c mice (a strain resistant to indu ction of experimental autoimmune encephalomyclitis), that after intravitrea l injection of any concentration of glutamate (a neurotransmitter that beco mes toxic when in excess) or ammonium-ferrous sulfate hexahydrate (which in creases the formation of toxic oxygen species), the loss of retinal ganglio n cells in mice devoid of mature T cells (nude mice) is significantly great er than in matched wild-type controls. We further show that this outcome ca n be partially reversed by supplying the T cell-defective mice with splenoc ytes, derived from the wild-type mice. The results suggest that potentially toxic physiological compounds, when present in excessive amounts, can recr uit and activate a T-cell-dependent self-protective immune mechanism. This may represent a prototype mechanism for the physiological regulation of pot entially destructive CNS events by T-cell-mediated immune activity, when th e local buffering mechanisms cannot adequately cope with them. (C) 2001 Els evier Science B.V.. All rights reserved.