Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

La Jolla Institute identifies molecular switch enabling immune cells to better fight disease

21.01.2013
Finding on killer cells opens new avenue for combating AIDS, cancer and other diseases

A research team led by the La Jolla Institute for Allergy & Immunology has discovered the mechanism that enables CD4 helper T cells to assume the more aggressive role of killer T cells in mounting an immune attack against viruses, cancerous tumors and other damaged or infected cells.

The finding, made in collaboration with researchers from the RIKEN Institute in Japan, could enable the development of more potent drugs for AIDS, cancer and many other diseases based on using this mechanism to trigger larger armies of killer T cells against infected or damaged cells.

CD4 helper T cells, which normally assist other cells of the immune system during an infection, and CD8 killer T cells, which directly attack and eliminate infected cells, are two of the body's most important immune cells for defending against diseases. Earlier research studies have shown that helper T cells can become killer cells in some instances. However, the specific mechanism of action that allowed this to occur was not known until now.

"We have identified the molecular switch that enables CD4 T cells to override their programming as helper cells and transform into cytolytic (killer) cells," said La Jolla Institute scientist and study co-leader Hilde Cheroutre, Ph.D. "Our team also showed that these transformed helper T cells represent a separate and distinct population of cells. They are not a subset of TH-1 helper cells as previously thought."

Jay A. Berzofsky, M.D., Ph.D., chief of the Vaccine Branch at the National Cancer Institute's Center for Cancer Research, called the finding "a major advance" that provides new understanding about the cell's lineage and basic mechanisms. Dr. Berzofsky was among the researchers whose work in the 1980s first demonstrated that helper cells could convert to killer cells. "Understanding how these cells derive and what causes them to switch from helper T cells to cytolytic T cells is an important step to learning how to manipulate them in disease," he said, noting it could lead to novel approaches "either to turn these cells off in autoimmune disease or turn them on in infectious diseases."

He added that the finding could also have important implications in cancer. "We need all of the cytolytic machinery that we can get to try to destroy cancers," he said. "If we can learn to turn them on, I think it's reasonable to believe that these cytolytic T cells can play an important role in controlling cancer."

The findings were published today in Nature Immunology in a paper entitled "Transcriptional reprogramming of mature CD4 helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes." Dr. Cheroutre is co-senior author on the study together with Dr. Ichiro Taniuchi of the RIKEN Research Center for Allergy and Immunology in Yokohama, Kanagawa, Japan. First authors on the paper are: Mohammad Mushtaq Husain, Ph.D., of the La Jolla Institute; Daniel Mucida, Ph.D., formerly of the La Jolla Institute, now at Rockefeller University; Femke van Wijk, Ph.D., formerly of the La Jolla Institute, now at the University Medical Center Utrecht, The Netherlands, and Sawako Muroi, of the RIKEN Institute.

Mitchell Kronenberg, Ph.D., La Jolla Institute president & chief scientific officer, said the study reflects the very successful collaboration between the La Jolla Institute and RIKEN in Japan, which have joined efforts on a number of projects over the years.

In the study, the researchers found that a certain transcription factor, which are molecules in the cell nucleus that control the activity of cells, continually suppresses the killer T cell lineage in helper T cells. Using mice, the team showed that turning off this transcription factor (ThPOK) enabled the helper cells in the body's peripheral areas, like the blood, spleen and the intestine, to override their original programming and to become killer T cells. "While our work focused on the intestines, we found that helper T cells in all tissues of the body have the potential to become killer cells in response to recognition of viral, tumor or other antigens in the context of cytokines such as IL-15," said Dr. Cheroutre.

Jonathan Braun, M.D., chair of the Department of Pathology and Laboratory Medicine at UCLA's David Geffen School of Medicine, praised the study as laying the groundwork for using T helper cells in a much more aggressive manner. "Helper T cells are mainly understood for their role in regulating other immune cells," he said. "This work reveals how they themselves can be triggered to become the action cells in the immune response. This opens new possibilities for how to manipulate them therapeutically in disease."

Dr. Cheroutre said the transformation of CD 4 helper T cells into killer cells already occurs in the body naturally. "Our finding could help to explain a number of occurrences that we haven't really understood up to this point, such as why some people can be chronically infected with HIV without developing AIDS." In these instances, Dr. Cheroutre is convinced that CD4 helper T cells must be taking over the role of killer cells after the CD8 T cells become exhausted. "It's like the helper cells can come in as reinforcements to keep the virus under control. If we can develop ways to artificially trigger that process, we may be able to significantly help people with HIV and other chronic infections."

While scientists would want to trigger a larger army of virus-specific killer cells in the case of infections, the opposite would be true in inflammation-fueled autoimmune diseases, like rheumatoid arthritis or multiple sclerosis, said Dr. Cheroutre. "The CD4 T cells are the bad wolves in inflammatory diseases because they often trigger more pro-inflammatory cells which worsen these conditions," she said. "With this knowledge, we may be able to prevent that by coaxing the CD4 killer cells to become regulatory cells instead, which is another one of their potential functions. In regulatory mode, the CD4 T cells suppress the immune system. This suppression reduces inflammatory cells, which is what we want to do in autoimmune diseases."

However in cancer, the CD4 T cell's regulatory function becomes problematic because they inhibit the killer T cells from destroying cancerous cells. This is because of their built-in mechanism to keep T cells from attacking the body's own cells, said Dr. Cheroutre. "Cancer cells develop from our own cells and only look a little different from healthy cells," she explained. "The killer T cells can sense that they are different and decide to eliminate them. However, the CD4 regulatory T cells frequently suppress the killer T cells and prevent them from destroying the cancerous cells. This is often how cancer cells can escape the immune system's normal action of stamping out bad cells."

Dr. Cheroutre said she believes it may be possible, using the newly discovered mechanism, to turn the CD4 regulatory T cells into killer cells that would aid, rather than block, the immune system's attack on cancerous cells.

About La Jolla Institute

Founded in 1988, the La Jolla Institute for Allergy & Immunology is a biomedical research nonprofit focused on improving human health through increased understanding of the immune system. Its scientists carry out research seeking new knowledge leading to the prevention of disease through vaccines and the treatment and cure of infectious diseases, cancer, inflammatory and autoimmune diseases such as rheumatoid arthritis, type 1 (juvenile) diabetes, Crohn's disease and asthma. La Jolla Institute's research staff includes more than 150 Ph.D.s and M.D.s. To learn more about the Institute's work, visit www.liai.org.

Bonnie Ward | EurekAlert!
Further information:
http://www.liai.org

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Starke IT-Sicherheit für das Auto der Zukunft – Forschungsverbund entwickelt neue Ansätze

Je mehr die Elektronik Autos lenkt, beschleunigt und bremst, desto wichtiger wird der Schutz vor Cyber-Angriffen. Deshalb erarbeiten 15 Partner aus Industrie und Wissenschaft in den kommenden drei Jahren neue Ansätze für die IT-Sicherheit im selbstfahrenden Auto. Das Verbundvorhaben unter dem Namen „Security For Connected, Autonomous Cars (SecForCARs) wird durch das Bundesministerium für Bildung und Forschung mit 7,2 Millionen Euro gefördert. Infineon leitet das Projekt.

Bereits heute bieten Fahrzeuge vielfältige Kommunikationsschnittstellen und immer mehr automatisierte Fahrfunktionen, wie beispielsweise Abstands- und...

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Mit Hilfe molekularer Schalter lassen sich künftig neuartige Bauelemente entwickeln

Einem Forscherteam unter Führung von Physikern der Technischen Universität München (TUM) ist es gelungen, spezielle Moleküle mit einer angelegten Spannung zwischen zwei strukturell unterschiedlichen Zuständen hin und her zu schalten. Derartige Nano-Schalter könnten Basis für neuartige Bauelemente sein, die auf Silizium basierende Komponenten durch organische Moleküle ersetzen.

Die Entwicklung neuer elektronischer Technologien fordert eine ständige Verkleinerung funktioneller Komponenten. Physikern der TU München ist es im Rahmen...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: GRACE Follow-On erfolgreich gestartet: Das Satelliten-Tandem dokumentiert den globalen Wandel

Die Satellitenmission GRACE-FO ist gestartet. Am 22. Mai um 21.47 Uhr (MESZ) hoben die beiden Satelliten des GFZ und der NASA an Bord einer Falcon-9-Rakete von der Vandenberg Air Force Base (Kalifornien) ab und wurden in eine polare Umlaufbahn gebracht. Dort nehmen sie in den kommenden Monaten ihre endgültige Position ein. Die NASA meldete 30 Minuten später, dass der Kontakt zu den Satelliten in ihrem Zielorbit erfolgreich hergestellt wurde. GRACE Follow-On wird das Erdschwerefeld und dessen räumliche und zeitliche Variationen sehr genau vermessen. Sie ermöglicht damit präzise Aussagen zum globalen Wandel, insbesondere zu Änderungen im Wasserhaushalt, etwa dem Verlust von Eismassen.

Potsdam, 22. Mai 2018: Die deutsch-amerikanische Satellitenmission GRACE-FO (Gravity Recovery And Climate Experiment Follow On) ist erfolgreich gestartet. Am...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

VideoLinks
Industrie & Wirtschaft
Veranstaltungen

Im Fokus: Klimaangepasste Pflanzen

25.05.2018 | Veranstaltungen

Größter Astronomie-Kongress kommt nach Wien

24.05.2018 | Veranstaltungen

22. Business Forum Qualität: Vom Smart Device bis zum Digital Twin

22.05.2018 | Veranstaltungen

VideoLinks
Wissenschaft & Forschung
Weitere VideoLinks im Überblick >>>
 
Aktuelle Beiträge

Berufsausbildung mit Zukunft

25.05.2018 | Unternehmensmeldung

Untersuchung der Zellmembran: Forscher entwickeln Stoff, der wichtigen Membranbestandteil nachahmt

25.05.2018 | Interdisziplinäre Forschung

Starke IT-Sicherheit für das Auto der Zukunft – Forschungsverbund entwickelt neue Ansätze

25.05.2018 | Informationstechnologie

Weitere B2B-VideoLinks
IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics