Discovery of new T-cell subtype opens window on rheumatoid arthritis

February 1, 2017, Brigham and Women's Hospital
arthritis
This is a hand afflicted by rheumatoid arthritis. Credit: The University of Manchester

A research team led by scientists from Brigham and Women's Hospital (BWH) has carefully scrutinized the immune cells from patients with rheumatoid arthritis, revealing a striking new subset of T-cells that collaborate with other immune cells to drive inflammation in peripheral tissues. The work, which was propelled by technologies that enable the detailed analysis of even a handful of cells, opens a critical window on the biology of the disease and suggests a strategy for the development of more precise, powerful treatments. The study appears in the February 1st advance online edition of the journal Nature.

"While the newest therapies for rheumatoid arthritis have helped transform our ability to treat the disease, they are fairly blunt instruments—blocking components of the immune system in a non-specific, global way," said first author Deepak Rao, who co-directs the Human Immunology Center at BWH. "Our results help illuminate a path toward treatments that are much more precise and focused only on the most relevant ."

Rheumatoid arthritis is an autoimmune condition in which the immune system attacks the joints, causing inflammation, pain, and eventually destruction of the tissues that make up this essential body part. The disorder affects roughly 1 percent of the world's population, and disproportionately afflicts women. Although there is significant evidence implicating T-cells—particularly their interactions with B-cells, which produce antibodies—it has been unclear which T-cell subtypes help orchestrate the damaging immune responses that underlie rheumatoid arthritis.

Rao, together with senior author Michael Brenner, set out to explore these questions by studying patient samples in remarkable detail not achieved in earlier studies. This "disease deconstruction" approach relies on sophisticated technologies, such as mass cytometry, which allowed the researchers to rapidly sift through blood, joint tissue, and the fluid surrounding joints to isolate specific cells, defined by the assortment of molecules on their surfaces. Rao and his colleagues also harnessed RNA sequencing methods that can characterize even very small numbers of cells, revealing which genes are turned on or off.

By using these and other high-tech tools, the researchers homed in on a unique population of T-cells that are highly prevalent in the joints of rheumatoid arthritis patients. These cells, a kind of CD4+ or "helper" T-cell, represent roughly one-quarter of the helper T-cells found in patients' joints. Yet abundance is not their only noteworthy attribute.

"These cells don't adhere to the conventional view of helper T-cells, and that is really interesting," said Rao.

By taking a deep look at these unique helper T-cells, Rao and his colleagues discovered that they display some unusual biological features. These T-cells are programmed to infiltrate parts of the body that are inflamed, and there they stimulate B-cells to produce antibodies. Antibodies are specialized proteins that usually recognize foreign substances and help rally the immune system to eliminate them. In autoimmune diseases, so-called autoantibodies instead recognize normal components of the human body and contribute to tissue damage. The Nature study represents the first detailed description of a type of T-cell with these features.

To extend their initial findings, the researchers seek to understand the signals that coax these cells to develop, and whether they play roles in other autoimmune diseases, such as lupus, multiple sclerosis, and type 1 diabetes. The BWH team also plans to explore whether targeting these unique T- hold promise as a treatment for .

"This work is a remarkable illustration of the power of our disease deconstruction approach," said Brenner, who also directs BWH's Human Immunology Center together with Rao. "We hope it will prove equally illuminating as we apply it to other immune-mediated diseases."

Explore further: Tracking movement of immune cells identifies key first steps in inflammatory arthritis

More information: Deepak A. Rao et al. Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis, Nature (2017). DOI: 10.1038/nature20810

Related Stories

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

January 20, 2017
Using a novel approach for imaging the movement of immune cells in living animals, researchers from the Massachusetts General Hospital (MGH) Center for Immunology and Inflammatory Diseases (CIID) have identified what appear ...

Early clinical trial success for new rheumatoid arthritis treatment

June 3, 2015
University of Queensland researchers have developed a world-first vaccine-style therapeutic approach to treat rheumatoid arthritis, a debilitating disease affecting more than 450,000 people in Australia.

Immune study offers treatment hope for arthritis patients

April 18, 2016
Arthritis and other inflammatory conditions could be helped by new insights into how the immune response is switched off.

New immune cell subset associated with progression to type 1 diabetes

October 11, 2016
A study conducted at the University of Eastern Finland revealed that a recently described T cell subset may have a central role in the development of type 1 diabetes. These so called follicular T helper cells were found to ...

Scientists find new potential target for rheumatoid arthritis

March 5, 2012
Newcastle University scientists, in work funded by Arthritis Research UK, have discovered a new way of potentially treating rheumatoid arthritis. This works by preventing damaging white blood cells cells from entering the ...

New strategy prevents rheumatoid arthritis in mice

February 8, 2013
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 ...

Recommended for you

Fetal immune system rejects the mother in preterm labor

April 25, 2018
Preterm labor, a common pregnancy complication, has long been a mystery to scientists. But a new study from UC San Francisco shows it may sometimes happen when the fetal immune system "wakes up" too early and begins to reject ...

Immune response might be stunting growth in millions of kids

April 24, 2018
An overactive immune system during childhood among young people in Ecuador's indigenous Shuar population comes with a cost: stunted growth.

Scientists unearth vital link between fat, immunity and heat regulation

April 24, 2018
Scientists have just made a surprising discovery involving fat and special immune cells that live within it—it turns out that 'gd T cells' are the key cogs in the biological wheel that regulates our body heat and protects ...

Odd one out: Protein goes against the family to prevent cancer

April 23, 2018
Melbourne researchers have made the surprise discovery that the 'odd one out' in a family of proteins known to drive cancer development is instead critical for preventing stomach cancers.

Research debunks 'myth' that strenuous exercise suppresses the immune system

April 20, 2018
New research overturns a myth that has persisted for nearly four decades - that competing in endurance sports, like this weekend's London Marathon, suppresses the body's immune system and makes competitors more susceptible ...

Immune diversity among the KhoeSan population

April 20, 2018
A new study of the KhoeSan of Southern Africa has improved the understanding of immune diversity among the oldest surviving indigenous population in the world.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.