Abstract

Resident memory T cells have emerged as key players in the immune response generated against a number of pathogens. Their ability to take residence in non-lymphoid peripheral tissues allows for the rapid deployment of secondary effector responses at the site of pathogen entry. This ability to provide enhanced regional immunity has gathered much attention, with the generation of resident memory T cells being the goal of many novel vaccines. This review aimed to systematically analyze published literature investigating the role of resident memory T cells in human infectious diseases. Known effector responses mounted by these cells are summarized and key strategies that are potentially influential in the rational design of resident memory T cell inducing vaccines have also been highlighted. A Boolean search was applied to Medline, SCOPUS, and Web of Science. Studies that investigated the effector response generated by resident memory T cells and/or evaluated strategies for inducing these cells were included irrespective of published date. Studies must have utilized an established technique for identifying resident memory T cells such as T cell phenotyping. While over 600 publications were revealed by the search, 147 articles were eligible for inclusion. The reference lists of included articles were also screened for other eligible publications. This resulted in the inclusion of publications that studied resident memory T cells in the context of over 25 human pathogens. The vast majority of studies were conducted in mouse models and demonstrated that resident memory T cells mount protective immune responses. Although the role resident memory T cells play in providing immunity varies depending on the pathogen and anatomical location they resided in, the evidence overall suggests that these cells are vital for the timely and optimal protection against a number of infectious diseases. The induction of resident memory T cells should be further investigated and seriously considered when designing new vaccines.

Highlights

  • Memory T cells have been subdivided into two broad categories: effector memory and central memory T cells (TEM and TCM, respectively)

  • The studies included in this review contain the most relevant findings related to immune responses generated by TRM against human pathogens, or make use of novel strategies for TRM generation

  • The investigators of this study report that circulating memory T cells were “barely recruited” when memory lymphocyte clusters (MLCs) were present in the mucosa

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Summary

Introduction

Memory T cells have been subdivided into two broad categories: effector memory and central memory T cells (TEM and TCM, respectively). Dubbed “Tissue-resident memory T cells” (here after referred to as TRM), this newly defined population exhibits the unique feature of remaining localized in peripheral tissues [1] As such, these cells provide enhanced localized immunosurveillance and protection of peripheral tissues when compared to TEM and TCM. Our understanding of TRM function is largely constrained within the context of infectious diseases As of it appears that TRM are better adapted to providing rapid protection against pathogen invasion when compared to their circulating counter parts [2,3,4]. Their ability to take residence in non-lymphoid peripheral tissues allows for the rapid deployment of secondary effector responses at the site of pathogen entry This ability to provide enhanced regional immunity has gathered much attention, with the generation of resident memory T cells being the goal of many novel vaccines

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