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 Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>