Detection and characterization of CD8+autoreactive memory Stem T cells in patients with type 1 diabetes

D Vignali, E Cantarelli, C Bordignon, A Canu, A Citro, A Annoni, L Piemonti, P Monti

Research output: Contribution to journalArticle

Abstract

Stem memory T cells (Tscm) constitute the earliest developmental stage of memory T cells, displaying stem cell-like properties, such as self-renewal capacity. Their superior immune reconstitution potential has sparked interest in cancer immune therapy, vaccine development, and immune reconstitution, whereas their role in autoimmunity is largely unexplored. Here we show that autoreactive CD8 + Tscm specific for β-cell antigens GAD65, insulin, and IGRP are present in patients with type 1 diabetes (T1D). In vitro, the generation of autoreactive Tscm from naive precursors required the presence of the homeostatic cytokine interleukin-7 (IL-7). IL-7 promotes glucose uptake via overexpression of GLUT1 and upregulation of the glycolytic enzyme hexokinase 2. Even though metabolism depends on glucose uptake, the subsequent oxidation of pyruvate in the mitochondria was necessary for Tscm generation from naive precursors. In patients with T1D, high expression of GLUT1 was a hallmark of circulating Tscm, and targeting glucose uptake via GLUT1 using the selective inhibitor WZB117 resulted in inhibition of Tscm generation and expansion. Our results suggest that autoreactive Tscm are present in patients with T1D and can be selectively targeted by inhibition of glucose metabolism. © 2018 by the American Diabetes Association.
Original languageEnglish
Pages (from-to)936-945
Number of pages10
JournalDiabetes
Volume67
Issue number5
DOIs
Publication statusPublished - 2018

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Type 1 Diabetes Mellitus
Stem Cells
T-Lymphocytes
Glucose
Interleukin-7
Active Immunotherapy
Hexokinase
Pyruvic Acid
Autoimmunity
Mitochondria
Up-Regulation
Insulin
Cytokines
Antigens
Enzymes
Neoplasms
Inhibition (Psychology)

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Detection and characterization of CD8+autoreactive memory Stem T cells in patients with type 1 diabetes. / Vignali, D; Cantarelli, E; Bordignon, C; Canu, A; Citro, A; Annoni, A; Piemonti, L; Monti, P.

In: Diabetes, Vol. 67, No. 5, 2018, p. 936-945.

Research output: Contribution to journalArticle

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AU - Bordignon, C

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AU - Citro, A

AU - Annoni, A

AU - Piemonti, L

AU - Monti, P

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