Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia

Abstract

MHC molecules are required for Ag recognition by T cells. Inasmuch as cells in the central nervous system do not express MHC constitutively, appearance of MHC, in inflammatory and degenerative diseases of the brain, may indicate local Ag presentation and subsequent immune response. Although both astrocytes and microglia are capable of class II MHC expression in vitro, in vivo studies failed to show the presence of significant amounts of class II on astrocytes compared to microglia. Our study is designed to clarify possible regulatory mechanisms that can explain the differences in inducibility of class II MHC between astrocytes and microglia in vivo. Using dissociated rat brain cell cultures, we have found that glutamate, an excitatory neurotransmitter, exerted a profound inhibitory effect on IFN-gamma-induced expression of class II on astrocytes, but not on microglia. Both glutamate and norepinephrine, a neurotransmitter previously reported to down-regulate class II on astrocytes, inhibited the induction of class II on astrocytes by eliminating accumulation of class II MHC mRNA. The kinetics of class II mRNA induction by IFN-gamma in the presence of glutamate suggested that glutamate may act as a transcriptional inhibitor. It is likely that class II induction on astrocytes in vivo may be selectively down-regulated by neurotransmitters such as glutamate and norepinephrine.