The finding that the tolerogenic effects of IL-2 on Tregs are TGF-β dependent and the non-redundant role of the NK-derived TGF-β on CD4+ Tregs have special clinical significance in immune-mediated disorders characterized by abnormal IL-2 and/or TGF-β production such as in SLE, where the production of IL-2 and TGF-β is decreased (11, 12). This evidence concerns the gene CD4 and systemic lupus erythematosus.