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Review
. 2023 Dec 13;214(3):249-259.
doi: 10.1093/cei/uxad090.

Tissue-Resident Memory T Cell: Ontogenetic Cellular Mechanism and Clinical Translation

Haoran Xu  1   2 , Runhong Zhou  1   2 , Zhiwei Chen  1   2   3
Affiliations
Review

Tissue-Resident Memory T Cell: Ontogenetic Cellular Mechanism and Clinical Translation

Haoran Xu et al. Clin Exp Immunol. .

Abstract

Mounting evidence has indicated the essential role of tissue-resident memory T (TRM) cells for frontline protection against viral infection and for cancer immune surveillance (Mueller SN, Mackay LK. Tissue-resident memory T cells: local specialists in immune defense. Nat Rev Immunol 2016, 16, 79-89. doi:10.1038/nri.2015.3.). TRM cells are transcriptionally, phenotypically, and functionally distinct from circulating memory T (Tcirm) cells. It is necessary to understand the unique ontogenetic mechanism, migratory regulation, and biological function of TRM cells. In this review, we discuss recent insights into cellular mechanisms and discrete responsiveness in different tissue microenvironments underlying TRM cell development. We also emphasize the translational potential of TRM cells by focusing on their establishment in association with improved protection in mucosal tissues against various types of diseases and effective strategies for eliciting TRM cells in both pre-clinical and clinical studies.

Keywords: T-cell differentiation; immunotherapy; mucosal immunity; tissue-resident memory T cell; vaccine.

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Conflict of interest statement

We declare no competing interests.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Tissue-resident memory T cells developed from naïve T cells and Tcirm. (A) Naïve T cell preconditioning and priming. During homeostasis, αV Integrin expressing migratory DC could activate latent TGF-β, which subsequently interacts with naïve CD8+ T cells. Preconditioned naïve T cells will preferentially develop into TRM after immune activation. After intravenously vaccinating adjuvanted peptide antigen, IL-10 released by blood monocytes acts in an autocrine mechanism to induce TGF-β production that in turn promotes TRM generation. (B) Circulating memory T-cell phenotypic switch. Circulating TEM will be recruited into inflamed lungs infected with the PR8 influenza virus and acquire the ability to develop into TRM during the memory phase. Batf3-dependent DCs could reactivate TCM, and the preconditioned reactivated cells will be biased to differentiate into skin TRM. Created with Biorender.com.
Figure 2.
Figure 2.
Clinical devices for inhaled vaccine. (A) FluMist and some ongoing clinical trials adopt Aerogen Ultra Device to deliver the intranasal vaccine. 200–500μL liquid containing vaccine component is nebulized via nasal inoculation. The issue is that large vaccine droplets easily attach to the upper respiratory mucosa and hardly reach to lungs. (B) An Ad5 COVID-19 vaccine utilizes Aerogen Ultra Device for vaccine inoculation. This administration procedure will last for 30–60 s and includes rounds of respiration which increases the exposure to vaccine particles in both upper respiratory mucosa and lung. Created with Biorender.com.
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