An autoimmune stem-like CD8 T cell population drives type 1 diabetes Journal Article

   


Authors: Gearty, S. V.; Dündar, F.; Zumbo, P.; Espinosa-Carrasco, G.; Shakiba, M.; Sanchez-Rivera, F. J.; Socci, N. D.; Trivedi, P.; Lowe, S. W.; Lauer, P.; Mohibullah, N.; Viale, A.; DiLorenzo, T. P.; Betel, D.; Schietinger, A.
Article Title: An autoimmune stem-like CD8 T cell population drives type 1 diabetes
Abstract: CD8 T cell-mediated autoimmune diseases result from the breakdown of self-tolerance mechanisms in autoreactive CD8 T cells1. How autoimmune T cell populations arise and are sustained, and the molecular programmes defining the autoimmune T cell state, are unknown. In type 1 diabetes, β-cell-specific CD8 T cells destroy insulin-producing β-cells. Here we followed the fate of β-cell-specific CD8 T cells in non-obese diabetic mice throughout the course of type 1 diabetes. We identified a stem-like autoimmune progenitor population in the pancreatic draining lymph node (pLN), which self-renews and gives rise to pLN autoimmune mediators. pLN autoimmune mediators migrate to the pancreas, where they differentiate further and destroy β-cells. Whereas transplantation of as few as 20 autoimmune progenitors induced type 1 diabetes, as many as 100,000 pancreatic autoimmune mediators did not. Pancreatic autoimmune mediators are short-lived, and stem-like autoimmune progenitors must continuously seed the pancreas to sustain β-cell destruction. Single-cell RNA sequencing and clonal analysis revealed that autoimmune CD8 T cells represent unique T cell differentiation states and identified features driving the transition from autoimmune progenitor to autoimmune mediator. Strategies aimed at targeting the stem-like autoimmune progenitor pool could emerge as novel and powerful immunotherapeutic interventions for type 1 diabetes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: controlled study; nonhuman; cd8+ t lymphocyte; animal cell; mouse; animal tissue; animal experiment; animal model; protein; cell fate; in vivo study; cell differentiation; rna; lymphocyte differentiation; t lymphocyte receptor; clonal variation; autoimmunity; insulin dependent diabetes mellitus; pancreas islet beta cell; transcriptome; diabetes; listeria monocytogenes; differentiation; emergence; diabetogenesis; cell component; male; female; article; stem cell self-renewal; induced response; single cell rna seq; draining lymph node; pancreatic draining lymph node
Journal Title: Nature
Volume: 602
Issue: 7895
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2022-02-03
Start Page: 156
End Page: 161
Language: English
DOI: 10.1038/s41586-021-04248-x
PUBMED: 34847567
PROVIDER: scopus
PMCID: PMC9315050
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85120356201&doi=10.1038%2fs41586-021-04248-x&partnerID=40&md5=d3ee0f20e2d028f6e4d4a214db18158f
Notes: Article -- Export Date: 1 March 2022 -- Source: Scopus
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MSK Authors
  1. Neeman Mohibullah
    16 Mohibullah
  2. Agnes Viale
    245 Viale
  3. Nicholas D Socci
    266 Socci
  4. Scott W Lowe
    251 Lowe
  5. Andrea Schietinger
    42 Schietinger
  6. Mojdeh Shakiba
    8 Shakiba
  7. Francisco Sanchez-Rivera
    29 Sanchez-Rivera
  8. Sofia Elena Vaccarino Gearty
    2 Gearty
  9. Prerak Mahendra Trivedi
    2 Trivedi
  10. Gabriel Espinosa Carrasco
    4 Espinosa Carrasco
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