The role of Ndfip1 in CD8+ T cell activation and effector function (121.25)

Abstract

Nedd4-family interacting protein 1 (Ndfip1) is an adapter protein for Nedd4-family E3 ubiquitin ligases. Mice lacking Ndfip1 in both CD4+ and CD8+ T cells develop a severe atopic inflammatory disease at sites of environmental exposure and die prematurely. In part, this is because Ndfip1 expression in CD4+ T cells is needed to inhibit IL-4 production and permit differentiation into non-Th2 lineages. However, Ndfip1-/- mice that lack MHC Class II-restricted CD4+ T cells still develop inflammation at a young age. This suggests that Ndfip1 might also be important in CD8+ T cells. We show that Ndfip1-/- CD8+ T cells are more sensitive to TCR stimulation than WT cells. After activation, Ndfip1-/- CD8+ T cells produce more IFN-γ than their WT counterparts. Consistent with this, Ndfip1-/- CD8+ T cells have higher levels of Eomesodermin than control cells. Future studies will attempt to identify E3 ligases and substrates that regulate these CD8+ T cell functions.