We have assessed how IL-2, an autoimmune diabetes susceptibility gene in both mouse and human, affects DC development. Using cultures of bone marrow cells stimulated with FMS-like tyrosine kinase 3 ligand (Flt3L), we have shown that IL-2 inhibits both cDC and pDC development. Furthermore, DCs that do develop in the presence of IL-2 display reduced ability to stimulate T cell proliferation. IL-2 is likely acting at the MDP stage because those are the precursors that express the IL-2Ra, and MDPs accumulate in cultures with Flt3L and IL-2. We are now assessing gene expression changes in DCs that develop in the presence of IL-2, comparing both the diabetes susceptible NOD mice to diabetes resistant B6 control mice.
