Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice.
Nat Commun 2016 Mar 15; 7:10991
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. Nat Commun 2016 Mar 15; 7:10991
Serr, Isabelle; Fürst, Rainer W; Achenbach, Peter; Scherm, Martin G; Gökmen, Füsun; Haupt, Florian; Sedlmeier, Eva-Maria; Knopff, Annette; Shultz, Leonard D.; Willis, Richard A; Ziegler, Anette-Gabriele; and Daniel, Carolin, "Type 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice." (2016). Faculty Research 2016. 52.