Unique Subset of Cells Team Up to Drive Rheumatoid Arthritis

Study opens doors for more precise RA treatments.

A subtype of CD4+ T cells join with B cells to help drive inflammation in the peripheral tissues—–the underlying cause of rheumatoid arthritis (RA).

RA affects approximately 1% of the world’s population, with most cases occurring in women. Prior studies have shown significant evidence that implicates T cells; however, precisely which T cell subtypes were involved was unclear.

In a study published in Nature, investigators used mass cytometry to analyze T cells in joint tissue obtained from patients with RA. This sophisticated technology allowed investigators to rapidly sift through blood, joint tissue, and the fluid surrounding the joints, to isolate specific cells.

The investigators also used RNA sequencing methods to characterize cells and identify which genes are turned on or off.

The results of the study showed a unique population of T cells that are highly prevalent in the joints of patients with RA. The cells are a subtype of CD4+ T cells, and account for about a quarter of the helper T cells found in the joints.

The investigators also found that the subset of T cells behaved in a different way than the other CD4+ T cells.

“These cells don’t adhere to the conventional view of helper T cells, and that is really interesting,” said first author Deepak Rao.

Using the “disease deconstruction” approach, the investigators discovered that the unique helper T cells are programmed to infiltrate parts of the body with inflammation. There, the T cells stimulated B cells to produce antibodies.

Normally, antibodies recognize foreign invaders and signal the immune system to rid the body of these substances. However, in individuals with autoimmune diseases, the antibodies mistake the normal components in the body and causes tissue damage.

“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,” Rao said. “Our results help illuminate a path toward treatments that are much more precise and focused only on the most relevant immune cells.”

The investigators plan to expand on their initial findings to determine which signals push the cells to develop, and whether they play a role in other autoimmune diseases, such as multiple sclerosis and lupus. Additionally, the team plans to examine whether targeting the unique T cells would prove a viable treatment for RA.

“This work is a remarkable illustration of the power of our disease deconstruction approach,” said senior author Michael Brenner. “We hope it will prove equally illuminating as we apply it to other immune-mediated diseases.”