In a discovery that is likely to rewrite immunology text books, researchers at the University of California (UC) Davis have found that early exposure to inflammatory cytokines, such as interleukin 2, can "paralyze" CD4 T cells, immune components that help orchestrate the body's response to pathogens and other invaders. This mechanism may act as a firewall, shutting down the immune response before it gets out of hand. However, from a clinical standpoint, this discovery could lead to more effective cancer immunotherapies, better drugs for autoimmune conditions, and new ways to expedite recovery from sepsis. The research was published in the August 18, 2015 issue of the journal Immunity. The article is titled “Out-of-Sequence Signal 3 Paralyzes Primary CD4+ T-Cell-Dependent Immunity.” "There's a three-signal process to activate T cells, of which each component is essential for proper activation," said first author Dr. Gail Sckisel, a post-doctoral fellow. "But no one had really looked at what happens if they are delivered out of sequence. If the third signal - cytokines - is given prematurely, it basically paralyzes CD4 T cells." To be activated, T cells must first recognize an antigen, receive appropriate co-stimulatory signals, and then encounter inflammatory cytokines to expand the immune response. Until now, no one realized that sending the third signal early - as is done with some immunotherapies - could actually hamper overall immunity. "These stimulatory immunotherapies are designed to activate the immune system," said Dr. Sckisel, "but considering how T cells respond, that approach could damage a patient's ability to fight off pathogens.
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