More MS news articles for Oct 2001

Researchers discover possible trigger for killer T cells to attack

9 October 2001

How do "killer T cells" know when to attack virus-infected and cancerous cells, and when to retreat? The answer possibly has been provided by Rockefeller University research to be published in the Nov. issue of Nature Immunology, and appearing online on Oct. 9. According to the report, the presence or absence of another set of immune system cells, called helper T cells, triggers the killer T cells to either attack or withdraw.

The new research may help scientists understand the breakdown in the immune system that leads to the development of lupus and other autoimmune diseases. Knowledge of how killer T cells are turned "on" or "off" ultimately may allow researchers to manipulate this switch for the treatment of these and other diseases.

"Our work demonstrates a new mechanism of killer T-cell regulation and suggests a novel therapeutic approach for shutting off these cells in patients with autoimmune disorders and in patients receiving organ or bone-marrow transplants," says Matthew Albert, M.D., Ph.D., first author of the paper and a clinical scholar at Rockefeller.

Killer T cells play a vital role in the immune system. When turned on or activated, they can target and destroy cancerous cells and cells harboring viruses. Specialized cells called dendritic cells present pieces of proteins or antigens to the killer T cells in order to alert them to the presence of the intruders. To perform this important function, however, the T cells first need to be taught about the body’s own proteins, such that potentially self-reactive T cells are prevented from killing the bodys own cells. This "education," or protein surveillance, occurs in the thymus gland, and is referred to by scientists as "tolerance."

But what about proteins not found in the thymus, for example those unique to the pancreas or skin? Recent studies in mice have shown that another round of education occurs in the various other tissues of the body, collectively known as the periphery. It is in these tissues that proteins not found in the thymus are scrutinized. Autoimmune diseases result from a breakdown in this overall education process.

The current paper proposes a new mechanism to explain how the T cells determine the path they should take. Previous research suggested that killer T cells are activated by two specific molecular signals.

The new theory, however, proposes that a third signal - helper T cells - acts like a switch to trigger the T-cell activation pathway. Helper T cells are known to play a role in the production of antibodies, a function of the immune system. Scientists thought that these cells also aided killer T cells in some way, but this role was unclear until now. Knowledge of this switch may ultimately lead to new ways of manipulating the immune system for the treatment of several diseases. For example, to treat autoimmune diseases or improve organ and bone- marrow transplant procedures, the goal would be to switch off the killer T cells that are erroneously attacking healthy cells.

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