The immune system’s ability to remember defeated disease-causing germs and avoid repeat infections is still poorly understood, but new research published in the journal Science Immunology clarifies an important piece of the picture.
The Rutgers University researchers employed specially bred mice to distinguish the roles of two types of immune cells known as tissue-resident memory T cells (Trm cells), which protect against infection and cancer. Their work may help improve vaccine efficacy and combat 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,” said Tessa Bergsbaken, an assistant professor at Rutgers New Jersey Medical School and the 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.”
Each new infection prompts the immune system to create customized T cells (a type of white blood cell) to protect itself. After the struggle is over, the immune system continues to produce those same T cells (although in much lower quantities) in case the invader returns.
Many T cells circulate throughout the body “looking” for the antigen they’re supposed to protect against, but Trm cells attach themselves in barrier tissues that separate the body from the outside world: skin, eyes, nasal passages, and the entire digestive tract. Previous research has revealed various subtypes of Trm cells, which are distinguished primarily by the expression of two specific proteins, CD103 and CD69. However, the functional differences between Trm subtypes remained a mystery.
For the study, researchers designed 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.”
Reference: “CD103 fate mapping reveals that intestinal CD103− tissue-resident memory T cells are the primary responders to secondary infection” by Helen Y. Fung, Matthew Teryek, Alexander D. Lemenze and Tessa Bergsbaken, 4 November 2022, Science Immunology.