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A novel humanized mouse model to study human antigen-specific cutaneous T cell responses in vivo

View ORCID ProfileMaria M. Klicznik, Ariane Benedetti, Laura M. Gail, Raimund Holly, Martin Laimer, Angelika Stoecklinger, Andreas Sir, Roland Reitsamer, Michael D. Rosenblum, Eva M. Murauer, View ORCID ProfileIris K. Gratz
doi: https://doi.org/10.1101/490060
Maria M. Klicznik
1Department of Biosciences, University of Salzburg, Salzburg, Austria
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Ariane Benedetti
1Department of Biosciences, University of Salzburg, Salzburg, Austria
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Laura M. Gail
1Department of Biosciences, University of Salzburg, Salzburg, Austria
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Raimund Holly
1Department of Biosciences, University of Salzburg, Salzburg, Austria
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Martin Laimer
2Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg, Austria
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Angelika Stoecklinger
1Department of Biosciences, University of Salzburg, Salzburg, Austria
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Andreas Sir
3Breast Center University Hospital of the Paracelsus Medical University Salzburg, Austria
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Roland Reitsamer
3Breast Center University Hospital of the Paracelsus Medical University Salzburg, Austria
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Michael D. Rosenblum
4Department of Dermatology, University of California, San Francisco CA 94143, USA
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Eva M. Murauer
1Department of Biosciences, University of Salzburg, Salzburg, Austria
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Iris K. Gratz
1Department of Biosciences, University of Salzburg, Salzburg, Austria
5Division of Molecular Dermatology and EB House Austria, Department of Dermatology, Paracelsus Medical University Salzburg, Austria
6Benaroya Research Institute, 1201 9th AVE, Seattle, WA 98101 USA
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Abstract

Human skin contains a significant number of 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. In this study we used immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered skin (ES) and received adoptively transferred human peripheral blood mononuclear cells. ES were generated from keratinocytes and fibroblasts only and initially contained no skin-resident immune cells. This reductionist system allowed us to study T cell recruitment and function in non-inflamed and non-infected human skin. We found that functional human T cells specifically infiltrated the human skin tissue and responded to microbial antigen in vivo. Importantly, T cell maintenance and function was supported by the microenvironment of human skin. We have thus generated a novel mouse model with broad utility in studies of human cutaneous antigen-specific T cell responses and the role of the skin microenvironment to skin immunity in vivo.

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Posted December 07, 2018.
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A novel humanized mouse model to study human antigen-specific cutaneous T cell responses in vivo
Maria M. Klicznik, Ariane Benedetti, Laura M. Gail, Raimund Holly, Martin Laimer, Angelika Stoecklinger, Andreas Sir, Roland Reitsamer, Michael D. Rosenblum, Eva M. Murauer, Iris K. Gratz
bioRxiv 490060; doi: https://doi.org/10.1101/490060
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A novel humanized mouse model to study human antigen-specific cutaneous T cell responses in vivo
Maria M. Klicznik, Ariane Benedetti, Laura M. Gail, Raimund Holly, Martin Laimer, Angelika Stoecklinger, Andreas Sir, Roland Reitsamer, Michael D. Rosenblum, Eva M. Murauer, Iris K. Gratz
bioRxiv 490060; doi: https://doi.org/10.1101/490060

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