A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin
| Autor: | Angelika Stoecklinger, Iris K. Gratz, Eva M. Murauer, Raimund Holly, Daniel J. Campbell, Jutta Horejs-Hoeck, Ariane Benedetti, Maria M. Klicznik, Suraj R Varkhande, Andreas Sir, Roland Reitsamer, Martin Laimer, Laura M Gail, Theresa Neuper, Michael Rosenblum |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Adoptive cell transfer Chemokine T-Lymphocytes medicine.medical_treatment T cell lcsh:Medicine Human skin Biology Immunological memory Article Mice Immune system Mice Inbred NOD Candida albicans medicine Animals Humans lcsh:Science Tissue homeostasis Skin Multidisciplinary Tissue Engineering lcsh:R Immunological surveillance Skin Transplantation Middle Aged Cell biology Experimental models of disease Cytokine medicine.anatomical_structure Humanized mouse biology.protein Heterografts Female lcsh:Q Immunologic Memory |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 IL2rγnull (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. |
| Databáze: | OpenAIRE |
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