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Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice.

Nat. Commun. 7:10991 (2016)
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Open Access Gold
Creative Commons Lizenzvertrag
Immune tolerance is executed partly by Foxp3(+)regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing β-cells. The development of autoantigen-specific vaccination strategies for Foxp3(+)Treg-induction and prevention of islet autoimmunity in patients is still in its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence for human autoantigen-specific Foxp3(+)Treg-induction in vivo. We identify HLA-DQ8-restricted insulin-specific CD4(+)T cells and demonstrate efficient human insulin-specific Foxp3(+)Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. Induced human Tregs are stable, show increased expression of Treg signature genes such as Foxp3, CTLA4, IL-2Rα and TIGIT and can efficiently suppress effector T cells. Such Foxp3(+)Treg-induction does not trigger any effector T cells. These T1D vaccine candidates could therefore represent an expedient improvement in the challenge to induce human Foxp3(+)Tregs and to develop novel precision medicines for prevention of islet autoimmunity in children at risk of T1D.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Regulatory T-cells; Class-ii Mhc; In-vivo; Nod Mice; Microneedle Patches; Immune-responses; High-risk; Insulin; Antigen; Tolerance
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 10991 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed