Study Differentiates Subtypes of Tissue-Resident Memory T Cells

Using specially bred mice, researchers at New Jersey’s Rutgers University have distinguished the functions of two types of tissue-resident memory T (Trm) cells, which protect against infection and cancer. The findings may help improve vaccine efficacy and lead to new treatments for a variety of autoimmune diseases.

“Understanding what each Trm cell type does allows us to formulate vaccines that generate the most effective type of Trm cell to combat a given infection, and our previous work suggests we can modify vaccines to shift the balance of these two cell types,” says Tessa Bergsbaken, an assistant professor at Rutgers New Jersey Medical School and senior author of the study. “Trm cells are not always beneficial. Certain autoimmune disorders can be driven by Trm cells, and we think what we’ve learned will also help us discover how these cells can turn against us.”

How the immune system remembers defeated disease-causing germs to prevent subsequent infections is not entirely understood. The Rutgers study, published recently in Science Immunology, clarifies an important piece of the picture—the functional differences between two Trm subtypes.

Each new infection leads the immune system to design custom T cells in defense. After the infection is cleared, the immune system keeps making those same T cells—albeit in much lower numbers—in case that specific invader returns.  While other T cells circulate throughout the body looking for the antigen they’re designed to guard against, Trm cells embed themselves in barrier tissues that separate the body from the outside world, including the skin, eyes, nasal passages and entire digestive tract.

Previous research has identified distinct subtypes of Trm cells and differentiated them largely by their expression of two specific proteins: CD103 and CD69.  To understand the functional differences between the two, the authors bred mice such that they could mark CD103+ Trm cells created in response to a common bacterial infection, Yersinia pseudotuberculosis. This, in turn, allowed them to differentiate the response of the CD103+ cells to reinfection from that of CD103- Trm cells.

They found that CD103+ cells didn’t multiply after reinfection or attack the invaders directly. Instead, it was the CD103- cells that multiplied upon reinfection and attacked the bacteria.

“What we saw was essentially a division of labor between these two distinct cells, but the CD103- Trm cells played a more important role,” Bergsbaken said. “Generating a higher number of these CD103- Trm cells during the initial infection or vaccination would likely result in better protection from a subsequent infection.”