Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

1,25-dihydroxyvitamin D3 and its Analogue TX527 Promote a Regulatory T Cell Phenotype in T Cells from Type 1 Diabetic Patients (#195)

Tom Van Belle 1 , Dorien Feyaerts 1 , Pierre Declercq 2 , Annemieke Verstuyf 1 , Conny Gysemans 1 , Chantal Mathieu 1
  1. Department of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
  2. Department of Organic Chemistry, Ghent University, Ghent, Belgium

The emergence of regulatory T cells as central mediators of peripheral tolerance in the immune system has led to an important area of clinical investigation to target these cells for the treatment of autoimmune diseases such as type 1 diabetes (T1D). Previous results from our lab have demonstrated that in vitro treatment of T cells from healthy individuals with TX527, a non-hypercalcemic analog of bioactive vitamin D3, can promote a CD4+CD25highCD127low regulatory profile and imprint a migratory signature specific for homing to sites of inflammation. Prior to consideration of vitamin D-induced regulatory T cells in autologous adoptive immunotherapy in the clinic, it is crucial to know whether this approach also works on T cells from human T1D patients. We show here that 1,25(OH)2D3 and TX527 imprinted T cells from T1D patients with a regulatory profile. 1,25(OH)2D3 exhibited a similar potency as TX527 to induce regulatory T cells and increases their expression of CTLA-4. Also, 1,25(OH)2D3 and TX527 treatment of human T cells inhibited the production of effector cytokines, such as IFN-γ, IL-17 and TNF-α. Importantly, 1,25(OH)2D3 and TX527 promoted, not only in control T cells but also in T1D T cells, the induction of IL-10-producing CD25highCD127low CD4+ T cells with the functional capacity to suppress proliferation of autologous responder T cells. We conclude that 1,25(OH)2D3 and TX527 are able to induce functional regulatory T cells in T cells from T1D patients.