Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Antibodies reverse type 1 diabetes in new immunotherapy study

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:

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

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>