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

More articles from Life Sciences:

nachricht Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie

nachricht How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel

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

Creating a new composite fuel for new-generation fast reactors

20.06.2018 | Materials Sciences

Game-changing finding pushes 3D-printing to the molecular limit

20.06.2018 | Materials Sciences

Could this material enable autonomous vehicles to come to market sooner?

20.06.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>