New defense mechanism against viruses, cancer identified

Scientists found a fundamentally new mechanism how our defense system is ramped up when facing a viral intruder; exploitation of this mechanism in vaccines sparks new hope for better prevention and therapy of infectious diseases and cancer. \"T killer cells\" (CD8 T cells) represent an important element of our body\'s defense system. They have the capacity to specifically identify and kill cells, which harbor viruses and bacteria or form a cancer. T killer cells would therefore represent an important component of yet unavailable vaccines against infections like HIV/AIDS, hepatitis C virus and malaria, and also for the treatment of cancer. It has been a longstanding observation that there is no match to the overwhelming T killer cell armada, which is triggered when a viral infection invades our body. Scientists had generally accredited this observation to \"pathogen-associated molecular patterns\" (PAMPs) on viruses and other microbes. PAMPs, i.e. the \"foreign look\" of viruses, alert so-called \"dendritic cells,\" which serve as policemen coordinating the T killer cell response. In a report now published in the journal Science, researchers led by Prof. Max L?hning (Charité-University Medicine & DRFZ Berlin) and Prof. Daniel Pinschewer (University of Geneva) describe an additional general mechanism by which viral infection triggers potent T killer cells: \"Dying virus-infected cells themselves ring the alarm bells to T killer cells.,\" Lohning said. Viruses cause infected cells to die, resulting in the release of cell components, which normally are not be visible to the outside -- analogous to an injured individual loosing blood. Such substances, heralding injury when released, are referred to as \"alarmins.\" The scientists found that T killer cells can sense an alarmin called \"interleukin 33\" (IL-33). IL-33 is contained in cells, which form the scaffold of the T killer cells\' home, the spleen and lymph nodes, and is released when such scaffold cells die. Mice lacking the gene encoding IL-33 failed to form a large T killer cell army upon viral infection. The few remaining cells had very poor fighting skills. Such mice were therefore exquisitely sensitive to several types of viral infections. Conversely, IL-33 could be used to artificially increase the T killer cell army, which was generated in response to vaccination. As Max Lohning and Daniel Pinschewer explain, PAMPs and alarmins apparently have complementary and non-redundant functions in shaping our T killer cell defense: \"The \"foreign look\" of viruses (PAMPs) activates the \"dendritic cell\" policemen to engage T killer cells. T killer cells, however, remain lousy fighters unless alerted by a cell death in their neighborhood (alarmins).\" These new findings could provide a key to effective vaccination against infectious diseases and cancer.