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Staying home or leaving for a party: tissue-dependent choices of tissue-resident memory T cells

Cellular & Molecular Immunology volume 19, pages 651–652 (2022)Cite this article

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CD8+ T cells differentiate into different types of memory T cells after priming in the lymphoid organs. Central memory T cells selectively express lymph node homing markers and recirculate between the blood and the secondary lymphoid organs. Effector memory T cells lack lymph node homing capacity, mainly circulate in the blood, and may enter peripheral tissues. The third subset consists of tissue-resident memory T (Trm) cells that express CD69 and adhesion molecules such as CD11a, CD103, and CD49a that prevent tissue egress. These Trm cells can be found throughout tissues and have important protective functions in infectious diseases as well as in malignancies. While it has been known for quite some time that Trm cells form rapid local recall responses, more recent studies indicate that upon secondary infection, Trm cells can also return to the blood and differentiate into circulating memory T-cell subsets [1, 2]. These studies indicate that Trm 1ells retain functional plasticity and that ex-Trm cells may contribute to systemic immunity.

Trm populations of skin, liver, small intestine, lungs, and other tissues are characterized by a specific set of transcription factors, including Runx3, Hobit, and Blimp-1, that control tissue exit [3]. Despite a common transcriptional signature, Trm cells in different tissues exhibit substantial diversity, as illustrated by the differential expression of certain surface receptors. CD103 is highly expressed by Trm cells in skin, where this TGFβ-induced adhesion receptor mediates binding to epithelial-expressed E-cadherin [4]. In contrast, liver Trm cells do not express CD103 but instead upregulate CD11a, which is essential for lodgment into the sinusoidal endothelium. A recent paper by Mackay and coworkers has shed new light on the diversity of skin and liver Trm cells and provides evidence that these Trm populations also have a different capacity to differentiate into circulating memory T cells [5].

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Authors and Affiliations

  1. Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066, CX, Amsterdam, The Netherlands

    Klaas P. J. M. van Gisbergen

  2. Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Joke M. M. den Haan

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  1. Klaas P. J. M. van Gisbergen
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Correspondence to Joke M. M. den Haan.

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van Gisbergen, K.P.J.M., den Haan, J.M.M. Staying home or leaving for a party: tissue-dependent choices of tissue-resident memory T cells. Cell Mol Immunol 19, 651–652 (2022). https://doi.org/10.1038/s41423-021-00828-z

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