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Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage
Type 1 diabetes (T1D) is an autoimmune disorder defined by CD8 T cell–mediated destruction of pancreatic β cells. We have previously shown that diabetogenic CD8 T cells in the islets of non-obese diabetic mice are phenotypically heterogeneous, but clonal heterogeneity remains relatively unexplored....
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170949/ https://www.ncbi.nlm.nih.gov/pubmed/35667687 http://dx.doi.org/10.26508/lsa.202201503 |
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author | Kasmani, Moujtaba Y Ciecko, Ashley E Brown, Ashley K Petrova, Galina Gorski, Jack Chen, Yi-Guang Cui, Weiguo |
author_facet | Kasmani, Moujtaba Y Ciecko, Ashley E Brown, Ashley K Petrova, Galina Gorski, Jack Chen, Yi-Guang Cui, Weiguo |
author_sort | Kasmani, Moujtaba Y |
collection | PubMed |
description | Type 1 diabetes (T1D) is an autoimmune disorder defined by CD8 T cell–mediated destruction of pancreatic β cells. We have previously shown that diabetogenic CD8 T cells in the islets of non-obese diabetic mice are phenotypically heterogeneous, but clonal heterogeneity remains relatively unexplored. Here, we use paired single-cell RNA and T-cell receptor sequencing (scRNA-seq and scTCR-seq) to characterize autoreactive CD8 T cells from the islets and spleens of non-obese diabetic mice. scTCR-seq demonstrates that CD8 T cells targeting the immunodominant β-cell epitope IGRP(206-214) exhibit restricted TCR gene usage. scRNA-seq identifies six clusters of autoreactive CD8 T cells in the islets and six in the spleen, including memory and exhausted cells. Clonal overlap between IGRP(206-214)–reactive CD8 T cells in the islets and spleen suggests these cells may circulate between the islets and periphery. Finally, we identify correlations between TCR genes and T-cell clonal expansion and effector fate. Collectively, our work demonstrates that IGRP(206-214)–specific CD8 T cells are phenotypically heterogeneous but clonally restricted, raising the possibility of selectively targeting these TCR structures for therapeutic benefit. |
format | Online Article Text |
id | pubmed-9170949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-91709492022-06-29 Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage Kasmani, Moujtaba Y Ciecko, Ashley E Brown, Ashley K Petrova, Galina Gorski, Jack Chen, Yi-Guang Cui, Weiguo Life Sci Alliance Research Articles Type 1 diabetes (T1D) is an autoimmune disorder defined by CD8 T cell–mediated destruction of pancreatic β cells. We have previously shown that diabetogenic CD8 T cells in the islets of non-obese diabetic mice are phenotypically heterogeneous, but clonal heterogeneity remains relatively unexplored. Here, we use paired single-cell RNA and T-cell receptor sequencing (scRNA-seq and scTCR-seq) to characterize autoreactive CD8 T cells from the islets and spleens of non-obese diabetic mice. scTCR-seq demonstrates that CD8 T cells targeting the immunodominant β-cell epitope IGRP(206-214) exhibit restricted TCR gene usage. scRNA-seq identifies six clusters of autoreactive CD8 T cells in the islets and six in the spleen, including memory and exhausted cells. Clonal overlap between IGRP(206-214)–reactive CD8 T cells in the islets and spleen suggests these cells may circulate between the islets and periphery. Finally, we identify correlations between TCR genes and T-cell clonal expansion and effector fate. Collectively, our work demonstrates that IGRP(206-214)–specific CD8 T cells are phenotypically heterogeneous but clonally restricted, raising the possibility of selectively targeting these TCR structures for therapeutic benefit. Life Science Alliance LLC 2022-06-06 /pmc/articles/PMC9170949/ /pubmed/35667687 http://dx.doi.org/10.26508/lsa.202201503 Text en © 2022 Kasmani et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Kasmani, Moujtaba Y Ciecko, Ashley E Brown, Ashley K Petrova, Galina Gorski, Jack Chen, Yi-Guang Cui, Weiguo Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage |
title | Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage |
title_full | Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage |
title_fullStr | Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage |
title_full_unstemmed | Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage |
title_short | Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage |
title_sort | autoreactive cd8 t cells in nod mice exhibit phenotypic heterogeneity but restricted tcr gene usage |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170949/ https://www.ncbi.nlm.nih.gov/pubmed/35667687 http://dx.doi.org/10.26508/lsa.202201503 |
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