Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Specialized regulatory T cell stifles antibody production centers

26.07.2011
Discovery has potential implications for cancer, autoimmune disease

A regulatory T cell that expresses three specific genes shuts down the mass production of antibodies launched by the immune system to attack invaders, a team led by scientists at The University of Texas MD Anderson Cancer Center reported online in the journal Nature Medicine.

"Regulatory T cells prevent unwanted or exaggerated immune system responses, but the mechanism by which they accomplish this has been unclear," said paper senior author Chen Dong, Ph.D., professor in MD Anderson's Department of Immunology and director of the Center for Inflammation and Cancer.

"We've identified a molecular pathway that creates a specialized regulatory T cell, which suppresses the reaction of structures called germinal centers. This is where immune system T cells and B cells interact to swiftly produce large quantities of antibodies," Dong said.

The discovery of the germinal center off-switch, which comes two years after Dong and colleagues identified the mechanisms underlying a helper T cell that activates the centers, has potential implications for cancer and autoimmune diseases.

"In some types of cancer, the presence of many regulatory T cells is associated with poor prognosis," Dong said. "The theory is those cells suppress an immune system response in the tumor's microenvironment that otherwise might have attacked the cancer."

However, in B cell lymphomas, overproliferation and mutation of B cells are the problems, Dong said. Hitting the regulatory T cell off-switch might help against lymphomas and autoimmune diseases, while blocking it could permit an immune response against other cancers.

Antibody production central

Germinal centers are found in the lymph nodes and the spleen. They serve as gathering points for B and T cell lymphocytes, infection-fighting white blood cells.

When the adaptive immune system detects an invading bacterium or virus, B cells present a piece of the invader, an antigen, to T cells. The antigen converts a naïve T cell to a helper T cell that secretes cytokines, which help the B cells expand and differentiate into specialized antibodies to destroy the intruder.

"Germinal centers have mostly B cells with a few helper T cells to regulate them. The B cells mutate to make high-affinity antibodies and memory B cells for long-term immunity. The cell population in the germinal center structures replicates in an average of several hours, one of the fastest rates of cell replication known in mammals," Dong said.

Tracking down specialized T cell

In the Nature Medicine paper, Dong and colleagues found that a subgroup of regulatory T cells that expresses two genes, Bcl-6 and CXCR5, moves into germinal centers in both mice and humans, where they have access to B cells.

(Bcl-6 produces a protein called a transcription factor, which moves into the cell nucleus to regulate other genes. CXCR5 is a receptor protein for a signaling molecule called CXCL13.)

They also found that the Bcl-6/CXCR5 T cells aren't produced in the thymus, with other T cells, but are generated by regulatory T cell precursor cells that express Foxp3, another transcription factor.

Knocking out the regulatory T cells that express all three proteins in mice resulted in increased germinal center production of antibodies. They named this key T cell the T follicular regulatory cell, or Tfr.

In a 2009 paper in the journal Science, the researchers found that naïve T cells that expressed Bcl-6 and CXCR5 also gathered in the B cell zone of germinal centers. Expression of Bcl6 converted the T cell into a T follicular helper (Tfh) cell that launches antibody production in the germinal centers.

With Tfr turning germinal centers off and Tfh turning them on, we could potentially regulate antibody production, Dong noted. Increasing Tfr production could be a new approach to treating autoimmune inflammatory disorders, such as lupus and rheumatoid arthritis.

The team's research was funded by grants from the National Institutes of Health, the Leukemia and Lymphoma Society, MD Anderson, the American Heart Association, Doris Duke Charitable Foundation Clinical Scientist Development Award and the China Ministry of Science and Technology Protein Science Key Research Project.

Co-authors with Dong are first author Yeonseok Chung, Ph.D., Shinya Tanaka, Ph.D., Roza Nurieva, Ph.D., Gustavo Martinez, Yi-Hong Wang and Joseph Reynolds, Ph.D., of MD Anderson's Department of Immunology and the Center for Cancer Immunology; Chung also is with The University of Texas Health Science Center at Houston Institute of Molecular Medicine; Seema Rawal and Sattva Neelapu, M.D., of MD Anderson's Department of Lymphoma and Myeloma, also of the Center for Cancer Immunology; and Ziao-hui Zhou, M.D., Hui-min Fan, M.D., and Zhong-ming Liu, M.D., of Shanghai Dong Fang Hospital, Shanghai, China.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For eight of the past 10 years, including 2011, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>