Tissue resident memory cells emerging as key player in health and disease

Abstract

Much of our understanding of the immune system has come from studying immune cells drawn from blood. Such samples are minimally invasive and relatively easy to collect, but they provide an incomplete and often misleading picture. Put simply, the biology of the immune system in blood doesn’t match the biology in the tissues where most infections play out, explains David Masopust, a Howard Hughes Medical Institute microbiologist at the University of Minnesota. “By basing concepts solely on blood and lymphoid populations, the field was missing out on a major part of the immune surveillance story,” says Masopust. Fig. 1. Virus-specific tissue-resident memory cells (red) patrol a mouse’s small intestine. Image courtesy of Sathi Wijeyesinghe (University of Minnesota, Minneapolis). In 2001, as a graduate student under the direction of the late Leo Lefrancois, chair of immunology at University of Connecticut, Masopust identified a group of immune cells that remain in the tissue after their encounter with a pathogen (1). He later dubbed them tissue resident memory (TRM) T cells. TRM cells, it seems, are qualitatively and functionally different from other immune cells. The notion that memory cells aren’t just circulating in the blood has changed the way we view the immune system, according to Masopust and other immunologists. The existence of TRMs—their location, physical and functional differences, and a still-emerging sense of their generation and maintenance—could help develop better vaccines and cancer immunotherapies. “TRMs are going to become a key component of the cancer immunotherapy conversation.” says Masopust. The classic paradigm of immunology entails two forms of immune defense. Innate immunity, a mix of antimicrobial chemicals and immune cells residing in barrier and other tissue, provides immediate but generic protection from pathogens. The innate immune response simultaneously releases chemical signals that trigger migration of T cells, part of the second line of defense, …