Human CD4<sup>+</sup>CD103<sup>+</sup> cutaneous resident memory T cells are found in the circulation of healthy subjects

Klicznik, Maria M.; Morawski, Peter A.; Höllbacher, Barbara; Varkhande, Suraj; Motley, Samantha; Kuri-Cervantes, Leticia; Goodwin, Eileen; Rosenblum, Michael D.; Long, S. Alice; Brachtl, Gabriele; Duhen, Thomas; Betts, Michael R.; Campbell, Daniel; Gratz, Iris K.

doi:10.1101/361758

Cited by 20 publications

(25 citation statements)

References 64 publications

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“…Upon entering the ES, CD4+ T cells upregulated CD69 expression ( Fig. 3d,e), a marker closely associated with tissue residency of human skin CD4+ T cells 25. Consistent with this, these skin-homing CLA+CD4+ T cells expressed CCR6 a receptor expressed by tissue-resident memory cells 54 (Fig. 3d,f).…”

Section: Engrafted T Cells Share a Skin-homing Memory-like Phenotypesupporting

confidence: 78%

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

Klicznik

Benedetti

Gail

et al. 2018

Preprint

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Human skin contains a population of memory T cells that support tissue homeostasis and provide protective immunity. T cell function in human skin is difficult to study due to a lack of adequate in vivo models. Thus, we utilized immunodeficient NOD-scid IL2rγ null (NSG) mice that carried in vivo-generated engineered skin (ES) and received adoptively transferred human peripheral blood mononuclear cells to follow the migration and function of circulating human memory T cells in human ES in vivo. ES were generated from human keratinocytes and fibroblasts only and initially contained no skin-resident immune cells. This reductionist system allowed us to study human T cell recruitment into non-inflamed and non-infected human skin, reflecting physiological skin conditions. Circulating human memory T cells preferentially infiltrated the human ES and these had the diverse functional profiles of T cells found in fresh human skin. Importantly, the chemokine and cytokine microenvironment found in the ES closely resembled that of non-inflamed human skin, which supports T cell maintenance and function. Upon entering the ES T cells assumed a resident memory T celllike phenotype in the absence of infection and these cutaneous T cells were activated locally upon injection of Candida albicans that was presented by autologous monocyte derived dendritic cells within the human ES. In summary, we have generated a novel mouse model with broad utility in studies of the dynamics of human cutaneous memory T cell generation, antigen-specific memory T cell responses, and the role of the skin microenvironment to skin immunity in vivo.

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Section: Engrafted T Cells Share a Skin-homing Memory-like Phenotypesupporting

confidence: 78%

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

Klicznik

Benedetti

Gail

et al. 2018

Preprint

Self Cite

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“…However, these studies lacked the technology to examine migratory lymphocyte populations in detail, and the reported findings cannot necessarily be extended to humans or non-human primates (Beura et al, 2016). Only a limited number of studies have been conducted on lymphocyte trafficking via efferent lymph in humans (Buggert et al, 2018;Fox et al, 1984;Girardet and Benninghoff, 1977;Klicznik et al, 2019;Lemaire et al, 1998;Vella et al, 2019;Voillet et al, 2018). In contrast to these efforts, we used state-ofthe-art technology to map the entire immune system in TDL.…”

Section: Discussionmentioning

confidence: 99%

The Identity of Human Tissue-Emigrant CD8+ T Cells

Buggert

Vella

Nguyen

et al. 2020

Cell

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Lymphocyte migration is essential for adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies to date have been restricted to immunological analyses of blood and various tissues.We used an integrated approach to characterize tissue-emigrant immune cells in thoracic duct lymph (TDL). The prevalent immunocytes in human and non-human primate efferent lymph were T cells. Cytolytic CD8 + T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically discrete and selectively confined to the intravascular circulation, whereas non-cytolytic CD8 + T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Moreover, these anatomically distinct gene expression profiles were recapitulated at the level of individual clonotypes, suggesting parallel differentiation programs independent of the expressed antigen receptor. Our collective dataset provides an atlas of the migratory immune system and defines the nature of tissueemigrant CD8 + T cells that recirculate via TDL.

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“…However, these studies lacked the technology to examine migratory lymphocyte populations in detail, and the reported findings cannot necessarily be extended to humans or non-human primates (Beura et al, 2016). Only a limited number of studies have been conducted on lymphocyte trafficking via efferent lymph in humans (Buggert et al, 2018;Fox et al, 1984;Girardet and Benninghoff, 1977;Klicznik et al, 2019;Lemaire et al, 1998;Vella et al, 2019;Voillet et al, 2018). In contrast to these efforts, we used state-of-the-art technology to map the entire immune system in TDL.…”

Section: Discussionmentioning

confidence: 99%

The identity of human tissue-emigrant CD8⁺T cells

Buggert

Vella

Nguyen

et al. 2020

Preprint

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Lymphocyte migration is essential for human adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies to date have been restricted to immunological analyses of blood and various tissues. To address this issue, we used an integrated approach to characterize tissue-emigrant immune cells in thoracic duct lymph (TDL). In humans and non-human primates, lymphocytes were by far the most abundant immune lineage population in efferent lymph, and a vast majority of these lymphocytes were T cells. Cytolytic CD8+ T cell subsets were clonotypically discrete and selectively confined to the intravascular circulation, persisting for months after inhibition of S1P-dependent tissue egress by FTY-720. In contrast, non-cytolytic CD8+ T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Collectively, these data provide an atlas of the migratory immune system and define the nature of tissue-emigrant CD8+ T cells that recirculate via TDL.

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Human CD4⁺CD103⁺ cutaneous resident memory T cells are found in the circulation of healthy subjects

Cited by 20 publications

References 64 publications

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

The Identity of Human Tissue-Emigrant CD8+ T Cells

The identity of human tissue-emigrant CD8⁺T cells

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Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects

Cited by 20 publications

References 64 publications

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin

The Identity of Human Tissue-Emigrant CD8+ T Cells

The identity of human tissue-emigrant CD8+T cells

Contact Info

Product

Resources

About

Human CD4⁺CD103⁺ cutaneous resident memory T cells are found in the circulation of healthy subjects

The identity of human tissue-emigrant CD8⁺T cells