Immunosuppression-back to the future.

During the 1950s work on bone marrow transplantation for patients with aplastic anemia led to the search for means other than total body irradiation to prevent rejection of the bone marrow allograft. At the same time, it had become clear that lymphocyte proliferation was a prominent feature of the immune response against all kinds of antigens, including skin allografts. These two factors led us to test various chemical agents known to block the proliferation of leukemic lymphocytes for their ability to inhibit the immune response against soluble antigens and skin allografts. One compound, the antileukemic drug 6-mercaptopurine, was effective in both test systems. This drug and its sister compound azathioprine (which is mercaptopurine with an imidizaole ring instead of a sulfhydryl group on carbon 6) were soon applied to human allografting and the treatment of autoimmune diseases.