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% 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
‘A new subset of T-cells that collaborate with other immune cells to drive inflammation in peripheral tissues in rheumatoid arthritis have been identified by researchers.
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
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 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 immune cells."
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
"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
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-cells 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."