Tissue‐resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance

Abstract

A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (T ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of T cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function. Nevertheless, certain transcriptional programs are shared and appear as important unifying features for the overall population of T cells and tissue-resident lymphocytes. It is now widely appreciated that T cells are a critical component of our immune defense by acting as peripheral sentinels capable of rapidly mobilizing protective tissue immunity upon pathogen recognition. This function is of particular importance in anatomical sites that are not effectively surveilled by blood-borne memory T cells in absence of inflammation, such as neuronal tissues or epithelial compartments in skin and mucosae. Focusing on the well-characterized subtype of CD8 CD69 CD103 T cells, we will review current concepts on the generation, persistence and function of T cells and will summarize commonly used tools to study these cells. Furthermore, we will discuss accumulating data that emphasize localized T responses as an important determinant of tissue homeostasis and immune defense in the context of microbiota-immune interactions, persistent infections and cancer surveillance.

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

“…Importantly, the density of T RM cells within the tumor environment has been shown to predict for improved survival in a number of cancer types, including advanced‐stage melanoma . In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models . Furthermore, we have recently demonstrated that T RM cells can promote cancer‐immune equilibrium in mouse skin by keeping dispersed melanoma cells dormant over extended periods of time .…”

“…The population of tumor‐associated lymphocytes in many advanced cancers contains CD8 + T cells that express transcriptional hallmarks of tissue‐resident memory T (T RM ) cells, including a lack of expression of the transcription factor, Kruppel‐like factor 2 and, consequently, an absence of tissue‐exit receptors such as S1PR1 and CCR7 . T RM cells are sessile cells that permanently reside within tissues without recirculating around the body . In the epidermal layer of skin and other epithelial tissues, T RM cells commonly express surface markers such as CD69 and CD103 which discriminate them from recirculating memory T cells .…”

“…In the epidermal layer of skin and other epithelial tissues, T RM cells commonly express surface markers such as CD69 and CD103 which discriminate them from recirculating memory T cells . Importantly, T RM cells in skin are key mediators of localised protection from infection with viruses and other pathogens . However, T RM cells can also drive skin inflammation in the context of autoimmune diseases and tissue transplantation .…”

“…However, T RM cells can also drive skin inflammation in the context of autoimmune diseases and tissue transplantation . Emerging clinical data further suggest that T RM cells provide immune surveillance in a variety of human cancers . Importantly, the density of T RM cells within the tumor environment has been shown to predict for improved survival in a number of cancer types, including advanced‐stage melanoma .…”

Origins of CD4+ circulating and tissue‐resident memory T‐cells

“…T RM have limited recirculation out of tissues and serve as sentinels at sites of potential reinfection, where they coordinate the initial response to pathogens and provide a substantial boost to tissue immunity via direct antigen recognition and recruitment of circulating immune cells . The majority of studies on T RM have focused on CD8 + tissue‐resident lymphocyte differentiation, survival and function, while less is known about their CD4 + counterparts, which are also known to mediate antiviral responses . The relationship between circulating and tissue‐resident CD4 + memory T‐cell origins and T H effectors subsets is currently unknown.…”