Scientists at Benaroya Research Institute at Virginia Mason (BRI) are scrutinizing a newly identified population of human immune cells in the blood that appear to have everything in common with infection-fighting T cells isolated from the skin.

The findings, published today in the journal Science Immunology, challenge current thinking that tissue-resident memory T cells are strictly retained in the tissue, in this case the skin. Further, the presence of a specific protein, CD69, appears to control whether these T cells are retained in the skin or migrate away.

BRI Principal Investigator Daniel Campbell, PhD, in partnership with scientists at the University of Salzburg in Austria, the University of Pennsylvania and other research institutions, demonstrated that T cells that were previously assumed to stay in the skin, and are referred to as tissue-resident memory T cells, can exit skin tissue, enter the blood and circulate throughout the body. These T cells can then relocate into skin at other locations of the body.

“Immunologists have largely thought once cells like these went to the skin, they would be locked in place and stay there forever, but now we find some are capable of re-entering the bloodstream,” Campbell said. “We think these migrating cells can use blood as a highway to spread immunity to different parts of the skin all over the body,” he said.

By studying these T cells in more detail, Campbell and colleagues found that the migration of the T cells likely plays a role in the healing of skin wounds and the ability to recognize and protect against infection. “Once these cells have battled an infectious agent at one site on the skin, they may be able to recognize and fend off infection at other sites and in subsequent encounters,” Campbell said.

“One really neat thing about our work is that now you can study this population of skin immune cells in the blood, which is much less invasive than a skin biopsy and is much more broadly available,” he said. “This should further accelerate research into the biology of these cells.”

In addition to potential implications for treatment of wounds and skin infections, the identification of this cell population presents an opportunity to identify therapies for immune-related diseases that affect the skin, including scleroderma, psoriasis and a form of lymphoma called mycosis fungoides.   

Steven F. Ziegler, PhD, who leads BRI’s immunology research program and directs the institute’s academic affairs, said that the results of Campbell’s work will open up new therapeutic areas for research into skin repair and healing. “The discovery of this novel T cell subset by Dr. Campbell and his colleagues provides important insights into how cells traffic to and from the skin and identifies a cell type likely involved in the repair of damage to the skin,” he said.

“We need to learn more about how these migrating cells act, and what drives them out of the skin in the first place,” Campbell said. “Once we understand more, we may be able to manipulate the cells to promote protective immunity, tissue-repair responses and reversal of autoimmune diseases of the skin.”