Featured Research

from universities, journals, and other organizations

Immune Cell Entry Into Pancreatic Islets Key To Understanding Type 1 Diabetes Origins

Date:
October 9, 2009
Source:
St. Jude Children's Research Hospital
Summary:
Researchers have discovered how destructive immune cells gain access to insulin-producing cells and help cause diabetes.

St. Jude Children's Research Hospital investigators have discovered how destructive immune cells gain access to insulin-producing cells and help cause diabetes.

Related Articles


The finding points to possible new strategies to halt or prevent type I diabetes.

Working in mice, researchers demonstrated that to enter key areas of the pancreas known as the islets of Langerhans, immune cells known as T cells must recognize a marker on the surface of insulin-producing cells housed there. T cells play a key role in regulating immune response. Once inside the islets, T cells trigger the inflammation that can lead to destruction of the insulin-producing beta cells. The result is type I diabetes.

The report answers a fundamental question about the role of T cell entry and accumulation in the islets in development of type I disease, a disease that affects as many as 3 million Americans. The research appears in the October 16 edition of the journal Immunity. Dario Vignali, Ph.D., is the paper's senior author and vice chair of the St. Jude Immunology department.

The St. Jude results contradict a widely held theory that only a small percentage of T cells that infiltrate the islets were actively involved in causing type I diabetes. The old scenario held that most of the T cells found in the islets were recruited to the site by a small number of specialized T cells. Those recruited or bystander T cells were thought to play no role in causing diabetes. Furthermore, it was thought that any T cell could gain access to the islets.

"The new research argues that every T cell in the islet is important. What these T cells recognize that allowed them to gain access to the islets may provide us with clues as to what might be needed to prevent diabetes," Vignali said. "Understanding the molecular differences between the T cells in the islets and the T cells in the periphery might also start to tell us a lot about what it takes to make a T cell attack the beta cells and cause diabetes."

Without insulin to turn food into fuel for cells, patients develop type I diabetes and are left dependent on insulin injections, an insulin pump or in rare cases a pancreas transplant. Unlike the more common form of the disease, known as type II diabetes, type I diabetes usually affects children and is sometimes called juvenile diabetes. About 15,000 new cases are diagnosed annually in the United States. Even with treatment, patients with type I diabetes are at risk for blindness, kidney failure and other complications.

"This paper also presents a new clinical intervention strategy—blocking T cells from even getting into the islet cells in the first place," Vignali added.

If any T cell could enter the islets, then it would be less likely that there were any "special rules" for entering islets and thus nothing unique about entry into the islets that might be targeted by treatment, he explained.

Understanding how T cell access to islets is controlled also raises hopes for developing a therapy to re-educate the immune system to tolerate rather than attack the beta cells. The St. Jude research points to a new route into islet cells.

For this study, scientists used a technique Vignali's laboratory developed in 2006. The technique allows researchers to quickly modify T cell production in mice. Normally mice make millions of T cells that can recognize many different cells and microorganisms. Each T cell carries on its surface a receptor that recognizes and binds to just one specific antigen, or marker, on the surface of the T cell's intended target.

The modification technique allowed researchers to create strains of mice with only two types of T cells, each with different receptors. One population carried a receptor that recognized the insulin-producing beta cells and could cause diabetes. The other group was programmed to recognize a different antigen. Researchers reported they could not induce the latter group of T cells to enter the islets.

Then investigators created and tracked T cells with three types of receptors—receptors from T cells with a proven ability to enter islet cells and cause diabetes, those able to enter islets and cause inflammation, but not diabetes, and a third group of receptors with no connection to type 1 diabetes or islet cells. The scientists reported that none of the T cells, even those with a demonstrated ability to cause diabetes in mice, could induce bystander T cells to enter the islet cells.

Finally, investigators tracked T cells carrying receptors from mice that naturally developed type I diabetes. They created mice with 17 new T cell receptors, five from the spleen of diabetic mice and 12 from T cells isolated in the islets of those diabetic mice. If the islets control T cells entry, then islets in the new mouse strains would be infiltrated by T cells with islet-derived, but not spleen-derived, receptors.

That is what happened. "About 70 percent of the receptors that came from the islets could mediate T cell migration back into the islets, while none of the receptors that came from the spleen could do likewise," Vignali said. The islet-derived receptors were also linked to rapid development of diabetes, with one-third causing diabetes during the 10-week study.

Vignali said it is unclear if the findings will hold true for other autoimmune diseases, such as rheumatoid arthritis or Crohn's disease. The authors noted that the structure, location and other factors might make the islet cells unique.

Greig Lennon, Maria Bettini and Amanda Burton, of St. Jude, shared first authorship on this study. The other authors were Erica Vincent and Paula Arnold of St. Jude, and Pere Santamaria of the University of Calgary, Alberta, Canada.

The work was supported in part by the Juvenile Diabetes Research Foundation International, the National Institutes of Health and ALSAC.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Immune Cell Entry Into Pancreatic Islets Key To Understanding Type 1 Diabetes Origins." ScienceDaily. ScienceDaily, 9 October 2009. <www.sciencedaily.com/releases/2009/10/091008123229.htm>.
St. Jude Children's Research Hospital. (2009, October 9). Immune Cell Entry Into Pancreatic Islets Key To Understanding Type 1 Diabetes Origins. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2009/10/091008123229.htm
St. Jude Children's Research Hospital. "Immune Cell Entry Into Pancreatic Islets Key To Understanding Type 1 Diabetes Origins." ScienceDaily. www.sciencedaily.com/releases/2009/10/091008123229.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins