Thomas Kupper

Thomas Kupper, MD, chair of the BWH Department of Dermatology, and colleagues have investigated the generation, localization and function of central memory T (TCM) cells and resident memory T (TRM) cells – both of which play important roles in protective immunity. The team’s findings are published in Nature Medicine.

In order to better understand the origin of these T cells, the authors immunized mouse skin with a protein, a virus, and a chemical, essentially training the mouse’s immune system to respond to each stimulus. Using high-throughput sequencing to analyze T cell receptor genes, the authors found that the same naive “parent” T cell gives rise to different populations of daughter cells – some that live in the skin, and protect the body from infection in that setting, and others that live in the lymph nodes and other parts of the body. This answered a fundamental and longstanding question in immunology: can one naive T cell give rise to only one type of cell, or to more than one. According to the authors, the research demonstrates that one naive T cell can differentiate along at least two different lineages simultaneously.

“It was a complete surprise to learn that the same precursor T cell gives rise to both the stationary TRM as well as T cells in lymph nodes (TCM), which freely circulate and provide a backup system for the immune response,” said Kupper, corresponding author of the study. “This is a bit like backing up your important computer files. These observations could never have been made without high throughput next generation sequencing.”

The authors also found that TRM cells mediated rapid contact hypersensitivity responses in mice – a model of human allergic contact dermatitis (ACD). The researchers then analyzed skin samples from human subjects with ACD, finding further evidence that TRM cells may play a critical role in the condition.

The authors note that their findings may have implications for other conditions in which the immune system goes awry. In skin, this may include psoriasis and vitiligo as well as ACD. In the gastrointestinal tract, TRM cells may be playing a role in Crohn’s disease, other inflammatory bowel disease and food allergy. Even autoimmune diseases like multiple sclerosis, rheumatoid arthritis and type I diabetes may involve pathological activation of these cells.

“We are learning that many diseases involving tissue immune responses are mediated by resident memory T cells (TRM),” said Kupper. “This has profound implications regarding disease treatment and management.”