When a patch of skin becomes inflamed—due to an infection or irritation—immune cells flock to the site to fight off any pathogens. Now, scientists have discovered that cells lodged in the skin keep the memory of such an infection for years afterward. The findings, reported in a new PNAS Early Edition paper, could lead to new ways to prevent or treat infections and chronic skin conditions.
“Knowing what we know about these cells now, we can potentially develop more effective vaccines,” says immunologist Scott Mueller of the University of Melbourne, a senior author of the new paper.
The presence of so-called skin-resident memory T cells was discovered by scientists only within the past decade. Memory T cells are generated after an infection, and retain the molecular marker of a pathogen. If that pathogen—a virus or bacteria—is encountered again, the memory T cells recognize it, and can launch a faster and more effective fight against it. For years, researchers thought that memory T cells only circulated in the blood. In 2004, multiple teams of scientists detected the presence of memory T cells within the skin and other epithelia, such as the lining of the lungs and stomach.
“Their location within tissues made it very hard for us to find them and to get them out to study,” says Mueller. “So they were basically overlooked.”
When they learned of the presence of the memory T cells in the skin, Mueller’s team wondered what happened to the skin-resident T cells after an infection cleared: did they remain in place, dissipate throughout the surrounding tissue, or disappear? To answer that question, the scientists closely observed sites of herpes simplex virus infections on the skin of mice, using molecular markers and microscopy. For months after the herpes infection disappeared, memory T cells that retained the signature of the herpes virus remained in place where the infection had been. Despite the ability for the cells to move, they didn’t dissipate away from the site as the researchers had expected.
“The discovery we made was that not only do they persist for long periods, but they persist right at where they were formed, at that site of the previous infection,” Mueller says. He expects that the memory T cells, in fact, remain at the site for the life of an organism.
The findings bring up a host of new questions about the function of the skin-resident memory T cells. “I think it’s pretty easy to guess why it would evolve to generate them in one site—if you get an infection in one spot, you might get it there again,” Mueller says. “I think the more interesting question is why it hasn’t evolved to then spread them out all over the skin in case you get an infection elsewhere.”
Mueller’s team is continuing to look at the biology of the unique memory T cells, studying whether they play key roles in other tissues of the body and why the skin-resident cells have a different physical appearance than other memory T cells. He also wants to know whether the immune cells lodged inside the skin are, at least partially, responsible for the constant inflammation associated with skin diseases like psoriasis and dermatitis. “This opens up all sorts of new avenues for studying diseases,” he says.