An autoimmune stem-like CD8 T cell population drives type 1 diabetes.
Nature
; 602(7895): 156-161, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34847567
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, ß-cell-specific CD8 T cells destroy insulin-producing ß-cells. Here we followed the fate of ß-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 ß-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 ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Linfócitos T CD8-Positivos
/
Diabetes Mellitus Tipo 1
/
Células Secretoras de Insulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nature
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos