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 processes, 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 functioning of the CNS, but become cytotoxic when their normal concentrations are exceeded. The CNS is equipped with buffering mechanisms that are specific for each compound. Here we show, using Balb/c mice (a strain resistant to induction of experimental autoimmune encephalomyelitis), that after intravitreal injection of any concentration of glutamate (a neurotransmitter that becomes toxic when in excess) or ammonium-ferrous sulfate hexahydrate (which increases the formation of toxic oxygen species), the loss of retinal ganglion cells in mice devoid of mature T cells (nude mice) is significantly greater than in matched wild-type controls. We further show that this outcome can be partially reversed by supplying the T cell-defective mice with splenocytes derived from the wild-type mice. The results suggest that potentially toxic physiological compounds, when present in excessive amounts, can recruit and activate a T-cell-dependent self-protective immune mechanism. This may represent a prototype mechanism for the physiological regulation of potentially destructive CNS events by T-cell-mediated immune activity, when the local buffering mechanisms cannot adequately cope with them.