Cellular switch for controlling immune system

A finding by researchers at the La Jolla Institute for Allergy & Immunology (LIAI) has identified a previously unknown cellular mechanism that acts as an off switch for immune system function. The discovery could lead to the future development of new treatments for autoimmune diseases.

In autoimmune diseases, the immune system, which normally wards off invading viruses and bacteria, instead mistakenly attacks normal body tissues, leading to illness. "By understanding this cellular process for turning off immune system activity, we are hopeful this will lead to new treatments that will stop unwanted immune responses, such as those which occur in autoimmune diseases," said LIAI scientist Carl Ware, Ph.D., who co-led the study with LIAI researcher Chris Benedict, Ph.D. The research team also involved scientists from Rush Medical Center and Northwestern University in Chicago and Washington University in St. Louis.

The findings will be published September 13 in the Proceedings of the National Academy of Sciences in a paper entitled, "Evolutionarily Divergent Herpesviruses Modulate T cell activation by Targeting the Herpesvirus Entry Mediator Cosignaling Pathway."

In the study, the team of scientists looked at two members of the herpes family of viruses, cytomegalovirus and herpes simplex virus, because of their ability to lay dormant in the immune system without causing disease. "These viruses teach us how to manipulate the immune system," Dr. Ware said. "We found that these two very different viruses were attacking the same communication pathway in the immune system." By disrupting that pathway, the viruses were keeping T lymphocytes - which are white blood cells that fight disease - from communicating with other cells in the immune system.

Central in the viruses' ability to manipulate immune system communication was a cellular protein called the Herpesvirus Entry Mediator (HVEM), which the scientists found effectively worked as an "off and on switch" for immune responses. Several cellular proteins -- members of the tumor necrosis factor (TNF) family -- interact with HVEM to enable this immune system communication switch. HVEM is part of a larger TNF family of molecules involved in a wide variety of important immune system functions. Drugs targeted at the TNF family are prominent treatments against some autoimmune diseases, including rheumatoid arthritis, psoriasis and Crohn's disease.

The findings also have implications beyond autoimmune disease, including possible application in treatments for infectious diseases and cancer. "An important part of our findings is that HVEM can not only switch off immune system response but it can also switch it on," Dr. Ware said. "This may be valuable in fighting infectious disease, where the body needs a stronger immune response. It also could aid in prompting immune cells to attack cancerous cells."

Source: La Jolla Institute for Allergy and Immunology