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Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice
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Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice
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Journal Article
Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice
2016
Overview
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.
Type 1 diabetes is associated with the loss of self-tolerance to the insulin-producing β-cells in the pancreas. Here the authors show that vaccination with insulin mimetopes can induce human insulin-specific regulatory T cells to mediate tolerance in a humanized mouse model.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/31
/ 692/308
/ Adult
/ Animals
/ Antigens
/ Child
/ Diabetes
/ Diabetes Mellitus, Type 1 - drug therapy
/ Diabetes Mellitus, Type 1 - immunology
/ Female
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - immunology
/ Gene Expression Regulation - immunology
/ Hematopoietic Stem Cell Transplantation
/ Humanities and Social Sciences
/ Humans
/ Immune Tolerance - immunology
/ Insulin
/ Interleukin-2 Receptor alpha Subunit - genetics
/ Interleukin-2 Receptor alpha Subunit - immunology
/ Ligands
/ Lymphocyte Activation - immunology
/ Male
/ Mice
/ Peptides
/ Receptors, Immunologic - genetics
/ Receptors, Immunologic - immunology
/ Science
/ T-Lymphocytes, Regulatory - immunology
/ Vaccines
