All About Multiple Sclerosis

More MS news articles for June 2003

Vulnerability of Human Neurons to T Cell-Mediated Cytotoxicity

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12817020&dopt=Abstract

J Immunol. 2003 Jul 1;171(1):368-379
Giuliani F, Goodyer CG, Antel JP, Yong VW.
Departments of Oncology and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada. McGill University, Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada. Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

Axonal and neuronal loss occurs in inflammatory diseases of the CNS such as multiple sclerosis.

The cause of the loss remains unclear.

We report that polyclonally activated T cells align along axons and soma of cultured human neurons leading to substantial neuronal death.

This occurs in an allogeneic and syngeneic manner in the absence of added Ag, requires T cells to be activated, and is mediated through cell contact-dependent mechanisms involving FasL, LFA-1, and CD40 but not MHC class I.

Activated CD4(+) and CD8(+) T cell subsets are equally neuronal cytotoxic.

In contrast to neurons, other CNS cell types (oligodendrocytes and astrocytes) are not killed by T cells.

These results demonstrate for the first time the high and selective vulnerability of human neurons to T cells, and suggest that when enough activated T cells accumulate in the CNS, neuronal cytotoxicity can result through Ag-independent non-MHC class I mechanisms.