Nanotechnology Now

Our NanoNews Digest Sponsors


Heifer International

Wikipedia Affiliate Button

Home > Press > New strategy prevents rheumatoid arthritis in mice: Infusions of regulatory T cells turn off autoimmune attack on joints

Harvey Cantor, MD
Harvey Cantor, MD

Abstract:
Dana-Farber Cancer Institute scientists have demonstrated a new strategy for treating autoimmune disease that successfully blocked the development of rheumatoid arthritis in a mouse model. They say it holds promise for improved treatment of arthritis and other autoimmune disorders in people.

New strategy prevents rheumatoid arthritis in mice: Infusions of regulatory T cells turn off autoimmune attack on joints

Boston, MA | Posted on February 9th, 2013

The scientists report in the Journal of Clinical Investigation that infusing a highly specific type of cell that regulates immune responses into arthritis-prone mice shuts down the cascade of inflammation that damages tissues and joints.

The method worked best when the infusions of CD8+ Treg cells were given at the same time that the animals were injected with a protein that triggered the arthritis-causing autoimmune reaction. "We found we could almost completely inhibit the disease in this setting," said Harvey Cantor, MD, chair of the Department of Cancer Immunology and AIDS at Dana-Farber and the study's senior author.

Even when administered weeks after the disease was initiated, CD8+ Treg infusions combined with low doses of methotrexate a commonly used drug for rheumatoid arthritis were able to significantly slow the arthritis process, the scientists reported.

The new strategy also blocked disease progression when the scientists injected peptide antigens to expand the rodents' own pool of CD8+ Tregs, rather than infusing them from outside. Overall, the results "suggest that [these] strategies represent a promising therapeutic approach to autoimmune disorders," the researchers wrote.

The human immune system is a network of cells, tissues, and organs that, when functioning normally, attacks and destroys infections, viruses, parasites, and other foreign "invaders."

In autoimmune disorders, however, parts of the immune system attack the individual's own healthy cells and tissues the result of the immune forces failing to recognize "self" identifying tags on the body's cells.

An estimated 50 million Americans suffer from autoimmune disorders, which include rheumatoid arthritis, lupus, type 1 diabetes, multiple sclerosis, and celiac disease. At least 100 different autoimmune diseases have been identified, and are more common among women. The incidence of these diseases is rising in the United States for unknown reasons.

Rheumatoid arthritis is caused by inflammation throughout the body, attacking many tissues, especially the joints, frequently causing painful and deformed fingers and hands. About 1.5 million Americans are afflicted with rheumatoid arthritis. Drugs of several types, including corticosteroids, are given to reduce inflammation and slow the disease. The newest treatments are biologic agents, which block secreted chemicals called cytokines that carry out the misguided attacks. However, even with these agents which can have serious side effects rheumatoid arthritis treatment is often not optimal, said Cantor.

In contrast to these "downstream" players in the complex autoimmune cascade, the strategy described in the new report is aimed "upstream," where the attacks begin with overactive immune fighters, called T follicular helper cells, that mistakenly respond to "self" markers on healthy cells. These T cells can become chronically overactivated, spurring a continuous attack by antibodies on the body's tissues.

"Current treatment strategies that inhibit cytokines, such as TNF or IL-1 production, spare the upstream initiating events that continuously induce new effector T cells and cytokine secretion," noted Cantor. "We believe that targeting the CD4 T cells that initiate this cascade may be a more effective approach to rheumatoid arthritis therapy."

T regulatory cells, or Tregs, play an important role in turning off an immune response when it's no longer needed, such as after the body has repelled viral or bacterial invaders. Cantor previously found that certain Tregs, known as CD8+ Tregs, can recognize and eliminate overactive CD4 T helper cells that display a marker called Qa-1 in mice; the human equivalent is HLA-E.

In the new experiments, Cantor's team showed that these Qa-1-recognizing CD8+ Tregs could be recruited to kill off the subset of the harmful T helper cells causing arthritis "and exert strong inhibitory effects on disease progression." They found that CD8+ Tregs that recognized an Hsp60 molecule on the Qa-1 T helper cells were the most effective in eliminating the overreacting T cells. The researchers showed that administering the Hsp60 antigen to the mice triggered expansion of the CD8+ Tregs already present in the animals and slowed or stopped disease development.

Moving closer to clinical relevance, the researchers will test this approach in mice carrying human immune cells that provoke an autoimmune response.

Cantor said they are also studying the possibility of using nanoparticles coated with Qa-1/Hsp60 molecules to expand CD8+ Tregs as a more practical method that might be used someday for human therapeutic tests.

First author of the paper is Jianmei W. Leavenworth, PhD, of the Cantor laboratory.

The research was supported in part by a National Institutes of Health research grant (AI037562) and a collaborative research agreement with NovoNordisk A/G.

####

For more information, please click here

Contacts:
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Call us toll-free: (866) 408-DFCI (3324)
617-632-4090

Copyright © Dana-Farber Cancer Institute

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

AIM Photonics Announces Release of Process Design Kit (PDK) for Integrated Silicon Photonics Design August 25th, 2016

Semblant to Present at China Mobile Manufacturing Forum 2016 August 25th, 2016

Johns Hopkins scientists track metabolic pathways to find drug combination for pancreatic cancer August 25th, 2016

New electrical energy storage material shows its power: Nanomaterial combines attributes of both batteries and supercapacitors August 25th, 2016

Govt.-Legislation/Regulation/Funding/Policy

Johns Hopkins scientists track metabolic pathways to find drug combination for pancreatic cancer August 25th, 2016

New electrical energy storage material shows its power: Nanomaterial combines attributes of both batteries and supercapacitors August 25th, 2016

Light and matter merge in quantum coupling: Rice University physicists probe photon-electron interactions in vacuum cavity experiments August 24th, 2016

New theory could lead to new generation of energy friendly optoelectronics: Researchers at Queen's University Belfast and ETH Zurich, Switzerland, have created a new theoretical framework which could help physicists and device engineers design better optoelectronics August 23rd, 2016

Nanomedicine

Johns Hopkins scientists track metabolic pathways to find drug combination for pancreatic cancer August 25th, 2016

50 years after the release of the film 'Fantastic Voyage,' science upstages fiction: Science upstages fiction with nanorobotic agents designed to travel in the human body to treat cancer August 25th, 2016

Tunneling nanotubes between neurons enable the spread of Parkinson's disease via lysosomes August 24th, 2016

Nanoparticles that speed blood clotting may someday save lives August 23rd, 2016

Discoveries

Stretchy supercapacitors power wearable electronics August 25th, 2016

Johns Hopkins scientists track metabolic pathways to find drug combination for pancreatic cancer August 25th, 2016

New electrical energy storage material shows its power: Nanomaterial combines attributes of both batteries and supercapacitors August 25th, 2016

50 years after the release of the film 'Fantastic Voyage,' science upstages fiction: Science upstages fiction with nanorobotic agents designed to travel in the human body to treat cancer August 25th, 2016

Announcements

AIM Photonics Announces Release of Process Design Kit (PDK) for Integrated Silicon Photonics Design August 25th, 2016

Semblant to Present at China Mobile Manufacturing Forum 2016 August 25th, 2016

Johns Hopkins scientists track metabolic pathways to find drug combination for pancreatic cancer August 25th, 2016

New electrical energy storage material shows its power: Nanomaterial combines attributes of both batteries and supercapacitors August 25th, 2016

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







Car Brands
Buy website traffic