In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-07-07)
Abstract:
Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD- scid IL2rγ null (NSG) mice that carried in vivo - generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans . Interestingly, we found that CD69 + memory T cells produced higher levels of effector cytokines in response to Candida albicans , compared to CD69 - T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-020-67430-7
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2615211-3
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