Organiser's Note: This talk was cancelled by the presenter, and therefore no video is available.

Natural regulatory T cells escape thymic deletion and appear to serve as regulators or suppressors of autoimmune, auto-reactive immune responses. Two mechanisms for the development of autoimmunity have been postulated: (i) induction of effector T cell (T effector) responses by T-helper (CD4+) or Th17 cells and (ii) loss of regulatory T-cell response [1]. Re-establishment of the natural equilibrium in terms of immune response to autologous proteins may be critically important for immunological well-being. Conceptually, natural Treg induction may contribute to expansion of antigen-specific adaptive Tregs leading to re-establishment of immune equilibrium [2,3]. We have identified several highly promiscuous MHC Class II T cell epitopes in conserved Fc and framework regions of IgG that are capable of specifically activating CD4+CD25+FoxP3+ natural regulatory T cells (nTregs). Co-incubation of these regulatory T cell epitopes or "Tregitopes" with a range of autoantigens leads to a suppression of effector cytokine and chemokine secretion, reduced proliferation of effector T cells, and expansion of antigen-specific adaptive Tregs. The corresponding murine epitopes suppress in vivo immune response in mice [4]. Building on these observations, we are now evaluating whether Tregitopes can tip the balance towards tolerance, allowing them to be harnessed for induction of tolerance in transplantation, allergy, and autoimmunity.

1. Bluestone JA, Abbas AK: Natural versus adaptive regulatory T cells. Nat Rev Immu (2003) 3:253-257.

2. Reveille, JD. The genetic basis of autoantibody production. Autoimmun Rev. 2006;5(6):389-98.

3. Lopez M, Clarkson MR, Albin M, Sayegh MH, Najafian N. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol. 2006 Oct;17(10):2844-53. Epub 2006 Aug 16.

4. De Groot AS, Moise L, McMurry JA, Wambre E, Van Overtvelt L, Moingeon P, Scott DW, Martin W. Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes". Blood. 2008 Oct 15;112(8):3303-11.