Our data pinpoint a safety signal for systemic administration of IL-2 and challenges a long-held conceptual platform of type 1 and 2 cytokine antagonism by newly documenting the IL-2-dependent development of IL-13 and IFN-γ double-positive (IL-13+IFNγ+) CD8+ T cells in SLE. This evidence concerns the gene CD8A and systemic lupus erythematosus.