The Role of CD4+ Resident Memory T Cells in Local Immunity in the Mucosal Tissue - Protection Versus Pathology.

Kiyoshi Hirahara,Ami Aoki,Kota Kokubo,Toshinori Nakayama,Masahiro Kiuchi

doi:10.3389/fimmu.2021.616309

Kiyoshi Hirahara, Ami Aoki + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2021.616309

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Abstract

Memory T cells are crucial for both local and systemic protection against pathogens over a long period of time. Three major subsets of memory T cells; effector memory T (TEM) cells, central memory T (TCM) cells, and tissue-resident memory T (TRM) cells have been identified. The most recently identified subset, TRM cells, is characterized by the expression of the C-type lectin CD69 and/or the integrin CD103. TRM cells persist locally at sites of mucosal tissue, such as the lung, where they provide frontline defense against various pathogens. Importantly, however, TRM cells are also involved in shaping the pathology of inflammatory diseases. A number of pioneering studies revealed important roles of CD8+ TRM cells, particularly those in the local control of viral infection. However, the protective function and pathogenic role of CD4+ TRM cells that reside within the mucosal tissue remain largely unknown. In this review, we discuss the ambivalent feature of CD4+ TRM cells in the protective and pathological immune responses. We also review the transcriptional and epigenetic characteristics of CD4+ TRM cells in the lung that have been elucidated by recent technical approaches. A better understanding of the function of CD4+ TRM cells is crucial for the development of both effective vaccination against pathogens and new therapeutic strategies for intractable inflammatory diseases, such as inflammatory bowel diseases and chronic allergic diseases.

Highlights

Memory T cells are crucial for both local and systemic protection against pathogens over a long period of time
Memory T cells were originally classified into two subpopulations, effector memory T (TEM) cells and central memory T (TCM) cells, based on [1] the expression pattern of cell surface molecules, [2] the orientation to specific tissues and
TEM cells show the low expression of CCR7, a chemokine receptor that is crucial for homing to the secondary lymphoid organ and the low expression of the cell surface molecule CD62L

Summary

Frontiers in Immunology

The protective function and pathogenic role of CD4+ TRM cells that reside within the mucosal tissue remain largely unknown. Regardless, the functions of memory T cells are closely linked to their mobility in the body of the host In mucosal tissues, such as the skin and female reproductive tract, antigen-recognized CD8+ TRM cells produce IFN-g and TNF-a to recruit other immune cells and activate dendritic cells and NK cells [12,13,14]. In non-mucosal tissues, such as the brain and liver, CD8+ TRM cells reside in each organ and play crucial roles in the host defense against pathogens [20, 21].

THE EXPERIMENTAL TECHNIQUES USED TO IDENTIFY TRM CELLS IN VIVO

OF TRM CELLS

Findings

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