For instance, mice deficient in CTLA-4 (CTLA-4-/-) or treated with CTLA-4 inhibitors developed inflammatory and autoimmune diseases characterized by substantial lymphocyte infiltration and tissue damage including diabetes, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, pancreatitis, thyroiditis, systemic lupus erythematosus, and colitis (81). Here, CTLA4 is linked to autoimmune disease.