Monday, September 19, 2011

The liver can defend itself by eating immune cells

Normally, the body deploys cytotoxic T-lymphocytes to clear the body of unwanted cells or to defend it from bacteria and other pathogens. These so-called CD8+ lymphocytes have special equipment to for their destructive actions. Normally, when cells need to be cleared from the body, for example because they are cancerous or otherwise damaged, the CD8+ cells are able to do their work undisturbed. Liver cells, however, seem to have found an unusual way to fight back against the immune system. A study conducted in mice shows that liver cells, which are called hepatocytes, are able to eat the CD8+ immune cells and therefore escape destruction.

Before cytotoxic T-lymphocytes reach their activated state, they wander in our bloodstream and tissues as naive T-cells. They need external signaling in order to become killer cells. Apparently, what the liver does is signal the opposite to the lymphocytes, which causes the cells to remain in their naive and inactivated state. Then, surprisingly, the hepatocytes engulf the T-cells, causing destruction inside the liver cell. The two pictures above show how a cytotoxic T-lymphocyte is engulfed by a hepatocyte (left) and consequently internalized and destroyed (right). This process is highly surprising: normally, only certain cells from the immune system assert such behavior, which is mostly deployed to neutralize pathogens. One of the most famous "cell eaters" is the macrophage, a cell that is highly specialized in eating foreign material, such as bacteria.

The liver defense mechanism may explain why liver transplants have a lower rejection rate than other organs. In transplantation, the organ that is put inside the body will be recognized as foreign matter, causing activation of the immune system, which will subsequently want to get rid of the foreign cells. The way hepatocytes get around getting killed by the immune system might be a relevant research topic, as it might tell us how we can more effectively prevent rejection after transplantation. Normally, patients receive immunosuppresive drugs that  weaken our entire immune system. While this does render the body unable to launch an attack against the foreign organ, it also leaves us unprotected against pathogens that enter our body.

Not only hepatocytes are able to defend themselves against the immune system. A lot of cancer variants need to develop a way to escape from the immune system, in order to grow larger. They mostly defend themselves by hiding; launching a head-on assault against the lymphocytes is a rather unusual feat.

You might say this is a form of cellular mutiny, battling against the orders that have been given by the body.

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