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Quantifying in situ adaptive immune cell cognate interactions in humans

Two-photon excitation microscopy (TPEM) has revolutionized our understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. Recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape. W...

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Autores principales: Liarski, Vladimir M., Sibley, Adam, van Panhuys, Nicholas, Ai, Junting, Chang, Anthony, Kennedy, Domenick, Merolle, Maria, Germain, Ronald N., Giger, Maryellen L., Clark, Marcus R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474677/
https://www.ncbi.nlm.nih.gov/pubmed/30778242
http://dx.doi.org/10.1038/s41590-019-0315-3
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author Liarski, Vladimir M.
Sibley, Adam
van Panhuys, Nicholas
Ai, Junting
Chang, Anthony
Kennedy, Domenick
Merolle, Maria
Germain, Ronald N.
Giger, Maryellen L.
Clark, Marcus R.
author_facet Liarski, Vladimir M.
Sibley, Adam
van Panhuys, Nicholas
Ai, Junting
Chang, Anthony
Kennedy, Domenick
Merolle, Maria
Germain, Ronald N.
Giger, Maryellen L.
Clark, Marcus R.
author_sort Liarski, Vladimir M.
collection PubMed
description Two-photon excitation microscopy (TPEM) has revolutionized our understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. Recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape. We postulated that by capturing these features in fixed-tissue samples, we could quantify in situ adaptive immunity. Therefore, we used a deep convolutional neural network to identify fundamental distance and cell shape features associated with cognate help (Cell Distance Mapping, CDM). In mice, CDM was comparable to TPEM for discriminating cognate from non-cognate T cell:dendritic cell (DC) interactions. In human lupus nephritis, CDM confirmed that myeloid DCs present antigen to CD4(+) T cells and identified plasmacytoid DCs as an important antigen-presenting cell. These data reveal a new approach to study human in situ adaptive immunity broadly applicable to autoimmunity, infection, and cancer.
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spelling pubmed-64746772019-08-18 Quantifying in situ adaptive immune cell cognate interactions in humans Liarski, Vladimir M. Sibley, Adam van Panhuys, Nicholas Ai, Junting Chang, Anthony Kennedy, Domenick Merolle, Maria Germain, Ronald N. Giger, Maryellen L. Clark, Marcus R. Nat Immunol Article Two-photon excitation microscopy (TPEM) has revolutionized our understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. Recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape. We postulated that by capturing these features in fixed-tissue samples, we could quantify in situ adaptive immunity. Therefore, we used a deep convolutional neural network to identify fundamental distance and cell shape features associated with cognate help (Cell Distance Mapping, CDM). In mice, CDM was comparable to TPEM for discriminating cognate from non-cognate T cell:dendritic cell (DC) interactions. In human lupus nephritis, CDM confirmed that myeloid DCs present antigen to CD4(+) T cells and identified plasmacytoid DCs as an important antigen-presenting cell. These data reveal a new approach to study human in situ adaptive immunity broadly applicable to autoimmunity, infection, and cancer. 2019-02-18 2019-04 /pmc/articles/PMC6474677/ /pubmed/30778242 http://dx.doi.org/10.1038/s41590-019-0315-3 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Liarski, Vladimir M.
Sibley, Adam
van Panhuys, Nicholas
Ai, Junting
Chang, Anthony
Kennedy, Domenick
Merolle, Maria
Germain, Ronald N.
Giger, Maryellen L.
Clark, Marcus R.
Quantifying in situ adaptive immune cell cognate interactions in humans
title Quantifying in situ adaptive immune cell cognate interactions in humans
title_full Quantifying in situ adaptive immune cell cognate interactions in humans
title_fullStr Quantifying in situ adaptive immune cell cognate interactions in humans
title_full_unstemmed Quantifying in situ adaptive immune cell cognate interactions in humans
title_short Quantifying in situ adaptive immune cell cognate interactions in humans
title_sort quantifying in situ adaptive immune cell cognate interactions in humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474677/
https://www.ncbi.nlm.nih.gov/pubmed/30778242
http://dx.doi.org/10.1038/s41590-019-0315-3
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