Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lag-3 gene dampens immune responses by controlling regulatory T-cell function

20.10.2004


St. Jude/Johns Hopkins discovery suggests that manipulating levels of Lag-3 protein on T regulatory cells might prevent autoimmune diseases or amplify immune system attacks on cancer cells



The discovery that the Lag-3 gene acts as a brake to prevent immune system responses from running out of control solves a mystery that has puzzled researchers since the gene was discovered 14 years ago. A report on this discovery, from investigators at St. Jude Children’s Research Hospital and The Johns Hopkins Kimmel Cancer Center, is published in the October issue of the journal Immunity. The researchers solved the mystery of what Lag-3 does by showing that the gene permits so-called regulatory T cells to act as brakes on the immune system.

Regulatory T cells, which carry the Lag-3 protein on their surfaces, interfere with the action of effector T cells--the "warrior" cells that orchestrate attacks on specific targets in the body, such as cancer cells and microorganisms.


The finding could form the basis for new strategies for improving the efficacy of anti-cancer vaccines or preventing autoimmune diseases. Autoimmune diseases are those in which the immune system attacks specific tissues of a person’s own body as if they were foreign matter. The researchers showed that the ability of regulatory T cells to control an attack by effector T cells is substantially prevented or eliminated in the absence of Lag-3.

Both the effector and regulatory cells arise from the same populations of cells, called CD4+ T lymphocytes, according to Dario A. A. Vignali, Ph.D., associate member of St. Jude Immunology. Vignali is senior author of the Immunity report.

The Lag-3 gene is activated in some of the CD4+ cells during an immune system response, turning them into regulatory cells that put the brakes on the activity of their fellow CD4+ T cells that are launching the attack. "The braking action of regulatory T cells prevents the destructive effects of autoimmune diseases, such as diabetes type 1, which occurs when effector T cells mount an attack on the cells of the pancreas that produce insulin," Vignali said.

However, regulatory T cells can also block the beneficial activity of anti-tumor effector cells. This braking action could inhibit an immune system attack on cancer cells. "This study adds to the mounting evidence that regulatory T cells play a major role in dampening the immune system’s anti-tumor activity," said Charles Drake, M.D., Ph.D., assistant professor of Oncology at the Johns Hopkins Kimmel Cancer Center. "The identification of a specific molecule on the surface of these cells that we can block represents an exciting new opportunity to amplify the potency of immune-system-based cancer therapies. We’re actively pursuing the best strategy to test these findings in patients."

Drake is co-author of the paper.

In mouse studies, the researchers first showed that regulatory T cells can protect against a potentially lethal, large-scale immune system attack by effector T cells that ordinarily would have caused a fatal lung disease.

Next, the team used a technique called DNA array analysis to identify which genes in the CD4+ T cells are activated in cells that develop into regulatory T cells. The investigators found that the Lag-3 gene was "expressed" (being used by the cell to make protein) to a much greater extent in regulatory T cells than in effector T cells. The team then showed that inserting the Lag-3 gene into CD4+ T cells turned them into regulatory T cells. These newly minted regulatory T cells suppressed effector T cell activity.

In addition, the researchers showed that antibodies against the Lag-3 protein block this moderating effect of regulatory T cells on the effector T cells, allowing the effector cells to continue an aggressive attack. This finding provided further evidence that Lag-3 is a key protein on regulatory T cells that controls effector T cell function.

"The tumor-specific T cells generated by some anti-cancer vaccines are not very effective because regulatory T cells block their therapeutic activity," said Creg J. Workman, Ph.D., a postdoctoral researcher in Vignali’s lab and co-author of the paper. "But if researchers could block Lag-3 on regulatory T cells it might possible to free such vaccines to generate an especially aggressive attack on cancer cells." "We’d like to put that kind of control over immune function into the hands of physicians," Vignali said.

Bonnie Cameron | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>