Multiple sclerosis study reveals how killer T cells learn to recognize nerve fiber insulators

Misguided killer T cells may be the missing link in sustained tissue damage in the brains and spines of people with multiple sclerosis, findings from the University of Washington reveal. Cytoxic T cells, also known as CD8+ T cells, are white blood cells that normally are in the body's arsenal to fight disease.

Multiple sclerosis is characterized by inflamed lesions that damage the insulation surrounding nerve fibers and destroy the axons, electrical impulse conductors that look like long, branching projections. Affected nerves fail to transmit signals effectively.

Intriguingly, the UW study, published this week in Nature Immunology, also raises the possibility that misdirected killer T cells might at other times act protectively and not add to lesion formation. Instead they might retaliate against the cells that tried to make them mistake the wrappings around nerve endings as dangerous.

Scientists Qingyong Ji and Luca Castelli performed the research with Joan Goverman, UW professor and chair of immunology. Goverman is noted for her work on the cells involved in autoimmune disorders of the central nervous system and on laboratory models of multiple sclerosis.

Multiple sclerosis generally first appears between ages 20 to 40. It is believed to stem from corruption of the body's normal defense against pathogens, so that it now attacks itself. For reasons not yet known, the immune system, which wards off cancer and infection, is provoked to vandalize the myelin sheath around nerve cells. The myelin sheath resembles the coating on an electrical wire. When it frays, nerve impulses are impaired.

Depending on which nerves are harmed, vision problems, an inability to walk, or other debilitating symptoms may arise. Sometimes the lesions heal partially or temporarily, leading to a see-saw of remissions and flare ups. In other cases, nerve damage is unrelenting.

The myelin sheaths on nerve cell projections are fashioned by support cells called oligodendrocytes. Newborn's brains contain just a few sections with myelinated nerve cells. An adult's brains cells are not fully myelinated until age 25 to 30.

For T cells to recognize proteins from a pathogen, a myelin sheath or any source, other cells must break the desired proteins into small pieces, called peptides, and then present the peptides in a specific molecular package to the T cells.

Scientists had previously determined which cells present pieces of a myelin protein to a type of T cell involved in the pathology of multiple sclerosis called a CD4+ T cell. Before the current study, no cells had yet been found that present myelin protein to CD8+ T cells.

Scientists strongly suspect that CD8+ T cells, whose job is to kill other cells, play an important role in the myelin-damage of multiple sclerosis. In experimental autoimmune encephalitis, which is an animal model of multiple sclerosis in humans, CD4+ T cells have a significant part in the inflammatory response. However, scientists observed that, in acute and chronic multiple sclerosis lesions, CD8+T cells actually outnumber CD4+ T cells and their numbers correlate with the extent of damage to nerve cell projections. Other studies suggest the opposite: that CD8+T cells may tone down the myelin attack.