Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibodies reverse type 1 diabetes in new immunotherapy study

06.07.2012
Scientists at the University of North Carolina School of Medicine have used injections of antibodies to rapidly reverse the onset of Type I diabetes in mice genetically bred to develop the disease. Moreover, just two injections maintained disease remission indefinitely without harming the immune system.

The findings, published online ahead of print (June 29, 2012) in the journal Diabetes, suggest for the first time that using a short course of immunotherapy may someday be of value for reversing the onset of Type I diabetes in recently diagnosed people. This form of diabetes, formerly known as insulin-dependent diabetes mellitus, is an autoimmune disease in which the body's own immune T cells target and destroy insulin-producing beta cells in the pancreas.


This image shows T cells (red, green) not detected and insulin (blue) readily observed in pancreatic islets of antibody-treated (Right) VS.untreated (Left) diabetic NOD mouse. Credit: Tisch Lab, UNC-Chapel Hill

The immune system consists of T cells that are required for maintaining immunity against different bacterial and viral pathogens. In people who develop Type 1 diabetes, "autoreactive" T cells that actively destroy beta cells are not kept in check as they are in healthy people.

Senior study author Roland Tisch, PhD, professor of microbiology and immunology at UNC, said a need for effective immunotherapies also exists to treat Type 1 diabetes in people already living with the disease.

"Clinically, there have been some promising results using so-called depleting antibodies in recently diagnosed Type 1 diabetic patients, but the disease process is blocked for only a short period of time," Tisch said. "These antibodies don't discriminate between T cells normally required for maintaining immunity to disease-causing pathogens and the autoreactive T cells. Therefore T cells involved in maintaining normal immune function are also going to be depleted.

"You're getting some efficacy from immunotherapy but its only transient, it doesn't reverse the disease, and there are various complications associated with the use of these depleting antibodies."

Tisch said his UNC lab has been studying the use of certain "non-depleting antibodies." These bind to particular proteins known as CD4 and CD8 expressed by all T cells. Just as the name implies, when these non-depleting antibodies selectively bind to CD4 and CD8 they don't destroy the T cells; the overall numbers of T cells are unaffected.

With this in mind Tisch wanted to determine whether these non-depleting antibodies could have a therapeutic effect in the non-obese diabetic, or NOD mouse, an excellent model for human Type 1 diabetes.

The answer is yes. In some of the recently diagnosed NOD mice, blood sugar levels returned to normal within 48 hours of treatment. Within five days, about 80 percent of the animals had undergone diabetes remission, reversal of clinical diabetes.

"The protective effect is very rapid, and once established, is long-term," he said. "We followed the animals in excess of 400 days after the two antibody treatments, and the majority remained free of diabetes. And although the antibodies are cleared from within the animals in 2-3 weeks after treatment, the protective effect persists." The study showed that beta cells in the NOD mice had been rescued from ongoing autoimmune destruction.

In looking for the mechanism to explain how the therapy worked, the researchers found that the antibodies had a very selective effect on T cells that mediated beta cell destruction. After treatment, "all the T cells that we would normally see in the pancreas or in tissues associated with the pancreas had been purged," said Tisch. This despite the fact that the numbers of T cells found in other tissues and blood were unaffected.

The researchers also found an increase in the numbers of "immune regulatory" T cells. In the healthy individual, these regulatory T cells block autoimmunity, Tisch explained. "They protect us from the autoreactive cells that all of us have. And that's why most of us don't develop autoimmune diseases such as Type 1 diabetes."

"We've demonstrated that the use of non-depleting antibodies is very robust. We're now generating and plan to test antibodies that are specific for the human version of the CD4 and CD8 molecules."

UNC study coauthors with Tisch are first-author, Zuoan Li, (now at the University of Iowa); Ramiro Diz, Aaron Martin, Yves Maurice Morillon, Douglas E. Kline, (now at the University of Chicago); Li Li (now at Harvard Medical School); and Bo Wang.

Support for research came from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; and from the Juvenile Diabetes Research Foundation.

Les Lang | EurekAlert!
Further information:
http://www.unc.edu

Further reports about: Antibodies CD4-Rezeptor CD8 Diabetes NOD T cells autoimmune disease beta cells

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>