J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/305/12 $2.00
Volume 185 January 1997 305-316

Major Histocompatibility Complex (MHC) Class I Gene Expression in Single Neurons of the Central Nervous System: Differential Regulation by Interferon (IFN)- and Tumor Necrosis Factor (TNF)-

By H. Neumann, H. Schmidt, A. Cavalié, D. Jenne, and H. Wekerle

From the Department of Neuroimmunology, Max-Planck-Institute for Psychiatry, D-82152 Martinsried, Germany

This study examined the effect of the pro-inflammatory cytokines interferon- (IFN-) and tumor necrosis factor- (TNF-) on the induction of MHC class I-related genes in functionally mature brain neurons derived from cultures of dissociated rat hippocampal tissue. Patch clamp electrophysiology combined with single cell RT-PCR demonstrated that ~50% of the untreated neurons contained mRNA for MHC class I heavy chains, while, with few exceptions, the cells failed to transcribe 2-microglobulin and TAP1/TAP2 gene transcripts. No constitutive expression of MHC class I protein was detectable by confocal laser microscopy on the surface of neurons.

All neurons transcribed the -chain of the interferon-type II receptor (binding IFN-) along with the p55 receptor for TNF-. Sustained exposure to IFN- resulted in transcription of 2microglobulin and TAP1/TAP2 genes and MHC class I surface expression in a minor part of the neurons, but did not alter their electrophysiological activities as assessed by whole cell electrophysiology. Suppression of neuronal electric activity by the sodium channel blocker tetrodotoxin drastically increased to almost 100% IFN--mediated induction of MHC class I chains, of both TAP transporters, and of membrane expression of MHC class I protein. The effect of tetrodotoxin is at least partly reverted by the neurotransmitter glutamate.

In contrast to IFN-, treatment with TNF- did neither upregulate TAP1/TAP2 nor 2microglobulin gene expression, but induced MHC class I heavy chain gene transcription in all neurons. Consequently, no MHC class I molecules were detectable on the membranes of TNF--treated neurons.

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