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

Lack of suppressive capacity of CD4+CD25+CD127lowFOXP3+ regulatory T cells in IL-15 rich environments (#190)

Anke Theil 1 , Elke Wessendorf 1 , Carmen Wilhelm 1 , Ezio Bonifacio 1
  1. Preclinical Approaches to Stem Cell Therapy / Diabetes, DFG-Center for Regenerative Therapies Dresden, TU Dresden, Germany

Inefficient peripheral tolerance of autoreactive T cells maintained by CD4+CD25+FOXP3+ T regulatory cells (Treg) is thought to contribute to the pathogenesis of autoimmune diseases including type I diabetes (T1D). Uncontrolled activation and expansion of autoreactive T cells occurs in an IL-7 and Il-15 rich environment such as after pancreatic islet transplantation. We previously showed that IL-7 can also abrogate Treg function. Here, we further explored the possibility that IL-15 may affect the function of Treg. We found that IL-15 can  revert  the  anergic state of naïve Treg in the presence of  artificial  TCR stimulus. The persistent presence of IL-15 abrogated Treg mediated suppression of αCD3αCD28 bead induced T effector proliferation as well as antigen-driven and allogeneic responses of CD4+ and CD8+ T cells. Notably, the presence of IL-15 did not influence Treg suppression of CD69 and CD154 activation marker expression on activated T effector cells. We suggest that prolonged periods of homeostatic expansion with increased availability of IL-7 and IL-15 can temporarily release natural regulatory control on T cells thereby providing an additional mechanism for initiating and expanding autoreactive T cells. Our findings have implications for therapies involving lympho-depletion.