Furthermore, IL-2 has been shown to upregulate CTLA-4 (cytotoxic T-lymphocyte-associated protein 4; CD152), and CTLA-4-deficienciy leads to a fatal lymphoproliferative disease that is more aggressive than the lymphoproliferative disorders caused by either IL-2 or Fas deficiency [35]. This evidence concerns the gene CTLA4 and hyperinsulinemic hypoglycemia, familial, 4.