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© Charité | Wiebke Peitz

Press release

16.02.2012

Successful Basic Research on Defense against Infections and Cancer

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Scientists discover new defense mechanism

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Cells dying from an infectious virus alarm killer T cells. Dendritic cells infected with a virus deliver the first activation signal for killer T cells through their T-cell receptors. Scientists discovered, that virus infected, dying cells also alarm killer T cells. Due to the viral infection, dying cells release the alarmin interleukin-33. This second signal leads to the complete activation of killer T cells. They reproduce quickly and effectively kill the cells infected with the virus.

Research groups from Charité Universitätsmedizin Berlin and the University of Geneva have discovered a new way of improving vaccines against infectious diseases and for use in cancer therapies. Scientists have shown a basic new mechanism that stimulates the body’s own alarm signals in case of viral infection to animate the immune system to maximum performance.

Viral infections activate so-called killer T cells. These form an important part of the body’s defense. They can recognize and destroy cells that are infected with viruses or have degenerated into cancer cells. Thus, killer T cells would be an important mechanism in vaccines against HIV/AIDS, hepatitis C, malaria, and in cancer therapies. To date, there are no vaccines available for any of these diseases. Killer T cells are activated by dendritic cells. These coordinate the body’s immune response.

The German-Swiss research group, surrounding Prof. Max Löhning from Charité and Prof. Daniel Pinschewer from University of Geneva, has now discovered a second mechanism that indicates how a viral infection stimulates killer T cells to maximum performance. Prof. Löhning explains: “The virus-infected, dying cells ring the alarm bells to the killer T cells themselves.

"When viruses destroy infected cells, cell matter is released that is usually invisible to killer T cells. This matter includes so-called alarmins. The scientists have discovered that killer T cells recognize the alarmin interleukin-33. In case of cell death, the cells that form the framework of the spleen and lymph nodes and are in direct proximity to killer T cells, release this alarmin.

In experiments with mice, researchers determined that mice missing the interleukin-33 gene failed to generate large numbers of killer T cells upon viral infection. The few cells remaining were only barely active. Conversely, administering the relevant alarmin during vaccination led to a large increase in killer T cells. These new findings form an important basis for the development of effective vaccines against infectious diseases and for cancer therapies.

Links

Link to article:
http://www.sciencemag.org/content/early/2012/02/08/science.1215418.abstract

Link to clinic:
http://rheumatologie.charite.de/

Contact

Prof. Max Löhning
Medizinische Klinik mit Schwerpunkten Rheumatologie und Klinische Immunologie
Charité – Universitätsmedizin Berlin   
t: +49 30 2846 0760



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