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Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes
AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells of the pancreas. Progress in understanding the cellular and molecular mechanisms underlying the human disease has been hampered by a dearth of appropriate human experimental models. We pr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861360/ https://www.ncbi.nlm.nih.gov/pubmed/31511930 http://dx.doi.org/10.1007/s00125-019-04988-6 |
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author | Joshi, Kriti Elso, Colleen Motazedian, Ali Labonne, Tanya Schiesser, Jacqueline V. Cameron, Fergus Mannering, Stuart I. Elefanty, Andrew G. Stanley, Edouard G. |
author_facet | Joshi, Kriti Elso, Colleen Motazedian, Ali Labonne, Tanya Schiesser, Jacqueline V. Cameron, Fergus Mannering, Stuart I. Elefanty, Andrew G. Stanley, Edouard G. |
author_sort | Joshi, Kriti |
collection | PubMed |
description | AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells of the pancreas. Progress in understanding the cellular and molecular mechanisms underlying the human disease has been hampered by a dearth of appropriate human experimental models. We previously reported the characterisation of islet-infiltrating CD4(+) T cells from a deceased organ donor who had type 1 diabetes. METHODS: Induced pluripotent stem cell (iPSC) lines derived from the above donor were differentiated into CD14(+) macrophages and tested for their capacity to present antigen to T cell receptors (TCRs) derived from islet-infiltrating CD4(+) T cells from the same donor. RESULTS: The iPSC macrophages displayed typical macrophage morphology, surface markers (CD14, CD86, CD16 and CD11b) and were phagocytic. In response to IFNγ treatment, iPSC macrophages upregulated expression of HLA class II, a characteristic that correlated with their capacity to present epitopes derived from proinsulin C-peptide to a T cell line expressing TCRs derived from islet-infiltrating CD4(+) T cells of the original donor. T cell activation was specifically blocked by anti-HLA-DQ antibodies but not by antibodies directed against HLA-DR. CONCLUSIONS/INTERPRETATION: This study provides a proof of principle for the use of iPSC-derived immune cells for modelling key cellular interactions in human type 1 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-019-04988-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
format | Online Article Text |
id | pubmed-6861360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-68613602019-12-03 Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes Joshi, Kriti Elso, Colleen Motazedian, Ali Labonne, Tanya Schiesser, Jacqueline V. Cameron, Fergus Mannering, Stuart I. Elefanty, Andrew G. Stanley, Edouard G. Diabetologia Short Communication AIMS/HYPOTHESIS: Type 1 diabetes is an autoimmune disorder characterised by loss of insulin-producing beta cells of the pancreas. Progress in understanding the cellular and molecular mechanisms underlying the human disease has been hampered by a dearth of appropriate human experimental models. We previously reported the characterisation of islet-infiltrating CD4(+) T cells from a deceased organ donor who had type 1 diabetes. METHODS: Induced pluripotent stem cell (iPSC) lines derived from the above donor were differentiated into CD14(+) macrophages and tested for their capacity to present antigen to T cell receptors (TCRs) derived from islet-infiltrating CD4(+) T cells from the same donor. RESULTS: The iPSC macrophages displayed typical macrophage morphology, surface markers (CD14, CD86, CD16 and CD11b) and were phagocytic. In response to IFNγ treatment, iPSC macrophages upregulated expression of HLA class II, a characteristic that correlated with their capacity to present epitopes derived from proinsulin C-peptide to a T cell line expressing TCRs derived from islet-infiltrating CD4(+) T cells of the original donor. T cell activation was specifically blocked by anti-HLA-DQ antibodies but not by antibodies directed against HLA-DR. CONCLUSIONS/INTERPRETATION: This study provides a proof of principle for the use of iPSC-derived immune cells for modelling key cellular interactions in human type 1 diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-019-04988-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users. Springer Berlin Heidelberg 2019-09-12 2019 /pmc/articles/PMC6861360/ /pubmed/31511930 http://dx.doi.org/10.1007/s00125-019-04988-6 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Short Communication Joshi, Kriti Elso, Colleen Motazedian, Ali Labonne, Tanya Schiesser, Jacqueline V. Cameron, Fergus Mannering, Stuart I. Elefanty, Andrew G. Stanley, Edouard G. Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes |
title | Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes |
title_full | Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes |
title_fullStr | Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes |
title_full_unstemmed | Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes |
title_short | Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes |
title_sort | induced pluripotent stem cell macrophages present antigen to proinsulin-specific t cell receptors from donor-matched islet-infiltrating t cells in type 1 diabetes |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861360/ https://www.ncbi.nlm.nih.gov/pubmed/31511930 http://dx.doi.org/10.1007/s00125-019-04988-6 |
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